Influence of BPPV and Meniere's Disease on Cognitive Abilities: A Questionnaire-Based Study

The vestibular system connects the inner ear to the midbrain and subcortical structures and can affect cognition. Patients with vertigo often experience cognitive symptoms such as attention deficits, memory problems, and spatial perception difficulties. This study aimed to explore the cognitive impairments associated with Benign paroxysmal positional vertigo(BPPV) and Meniere's Disease(MD). A non-experimental group comparison design was used with 107 participants divided into three groups: Group I(clinically normal), Group II(BPPV), and Group III(MD). Participants completed a questionnaire with 10 cognition-related questions, and their responses were scored. The data were found to be non-normally distributed. The analysis revealed a significant difference in scores between Group I and both Group II and Group III. Chi-square tests showed that the responses to cognition-related questions varied among the groups, with Group II exhibiting more cognitive problems. Associated conditions like hypertension, diabetes, and hearing loss did not significantly influence the responses within each group. This study suggests a significant relationship between cognitive problems and patients with BPPV and MD. However, there was no association found between the cognitive problems experienced in BPPV and MD patients. These findings align with previous research indicating that vestibular disorders can lead to deficits in spatial memory, attention, and other cognitive functions. By understanding the link between cognition and vestibular disorders, we can improve diagnosis and rehabilitation services to enhance the quality of life for these patients.

Saccades of video head impulse test in Meniere's disease and Vestibular Migraine: What can we learn from?

Background:Saccades are often observed on video head impulse tests(vHIT)in patients with Meniere's Disease(MD)and Vestibular Migraine(VM).However,their saccadic features are not fully described.Objective:This study aims to identify the saccades characteristics of MD and VM.Methods:75 VM patients and 103 definite unilateral MD patients were enrolled in this study.First raw saccades were exported and analyzed.The VM patients were divided into left and right based on their ears,while the MD patients were separated into affected and unaffected subgroups based on their audiograms and symptoms.Results:The MD patients have more saccades on the affected side(85%vs.69%),and saccade velocity is more consistent than the contralateral side(shown by the coefficient of variation).The saccades occurrence rates on both sides are similar in VM(77%vs.76%),as are other saccadic parameters.The MD patients have more significant inter-aural differences than the VM patients,manifested in higher velocity(p-value 0.000),earlier arriving(p-value 0.010),and more time-domain gathered(p-value 0.003)on the affected side.Conclusions:Bilateral saccades are commonly observed in MD and VM.In contrast to MD,saccades on VM are subtle,scattered,and late-arrived.Furthermore,the MD patients showed inconsistent saccadic distribution with more velocity-uniform saccades on the affected side.

The role of cochlear implantation in alleviating Tumarkin drop attacks of Meniere's disease;a case report

Ménière’s disease(MD)patients may suffer episodes of sudden falls,named Tu markin drop attacks(DAs).This fall occurs abruptly and without warning or loss of consciousness.DAs usually aggravate the clinical picture of MD and are challenging to manage.The present report describes a case treated by cochlear implantation(CI)due to concomitant deafness and offers some clinical considerations for this condition.A male patient aged 48 years with a 10-year history of definite bilateral MD had profound SNHL on the right and severe SNHL on the left side.He suffered from intermittent attacks of vertigo,ear fullness,and tinnitus and,in the last year,had developed DAs and experienced 14 episodes in the previous six months.The preoperative category of acoustic performance was 3.The Dizziness Handicap Inventory(DHI)questionnaire showed a total score of 46,which indicated a moderate degree of disability.A CI was planned for the right side.The patient did not report any further DAs episode for two years since then.The postoperative category of acoustic performance became 11,and the postoperative DHI questionnaire showed a decrease in the total score(from 46 to 19),which indicated a mild disability.Unilateral CI effectively alleviated the DAs associated with bilateral MD.Our report proposes a new modality for managing vertiginous symptoms in cases of MD with hearing loss without the need for more aggressive surgical interventions with the need for clinical trials to confirm our results.

A study of efficacy of Nigella sativa in treatment of Meniere's disease: A randomized, placebo controlled clinical trial

Purpose:Meniere's disease(MD),first introduced by Prosper Meniere,is characterized mainly by vertigo,tinnitus,aural fullness and sensorineural hearing loss.Though the exact pathophysiology of MD is unknown,immunologic and inflammatory interactions are possible underlying mechanisms involved in MD.This study is aimed to investigate the immunomodulatory and anti-inflammatory effect of Nigella sativa on MD as a therapeutic agent.Methods:We divided 40 patients with definite MD into two groups of 20 cases.The study group received 1 g of Nigella sativa oil daily for three months and the control group received a placebo.Changes in hearing,tinnitus and vertigo were estimated by pure tone audiometry,tinnitus handicap inventory questionnaire and dizziness handicap inventory questionnaire,respectively.Results:At the end of the study we did not observe any significant improvement in study's group hearing threshold,tinnitus and vertigo compared to the control group.Conclusions:In this study,statistical analysis showed that Nigella sativa failed to improve signs and symptoms of MD.However,further investigations with a larger study population are needed to ascertain the current conclusion.

Dexamethasone does not affect endolymphatic hydrops(EH)in patients with Meniere's disease within 24 h,and intratympanic administration of gadolinium plus dexamethasone simplifies high-quality imaging of EH using a novel protocol of 7 min

Background:Intratympanic administration of gadolinium chelate allows for a better visualization of endolymphatic hydrops(EH)using MRI than intravenous injection and was recently further improved to facilitate high-quality imaging of EH in 7 min.The aim of the present study was to simplify the intratympanic administration protocol by mixing gadolinium chelate with therapeutic dexamethasone and to evaluate the effects of this mixture on the visualization of EH in MRI.Materials and methods:In an in vitro study,the potential impact of gadolinium-diethylenetriamine pentaacetic acid(Gd-DTPA)on the stability of dexamethasone was evaluated by analyzing dynamic changes in dexamethasone with high-performance liquid chromatography(HPLC)after mixing with GdDTPA.Ten patients with definite Meniere's disease(MD)were recruited to study the potential interference of dexamethasone on MRI visualization of EH,and 49 patients with MD were recruited to evaluate the effect of intratympanic injection of Gd-DTPA mixed with dexamethasone on MRI of EH using a 3T MR machine and a novel heavily T2-weighted 3-dimensional fluid-attenuated inversion recovery reconstructed using a magnitude plus zero-filled interpolation(hT2FLAIR-MZFI)sequence.Results:The retention times and peak area of dexamethasone in HPLC were not modified by the addition of Gd-DTPA.EH grading in the cochlea and vestibule was not influenced in any ear by intratympanic injection of dexamethasone.Excellent inner ear images were obtained from all patients,and EHs with various grades were displayed.There were significant correlations between diagnosis and cochlear EH(p<0.01,Spearman's Rho),between diagnosis and vestibular EH(p<0.01,Spearman's Rho),and between cochlear and vestibular EH(p<0.01,Spearman's Rho).The distribution of Gd-DTPA plus dexamethasone negatively correlated with the grade of vestibular EH.Injury of the endolymph-perilymph barrier was detected in one cochlea and three vestibules of 59 inner ears with MD.Conclusions:Intratympanic administration of Gd-DTPA plus dexamethasone yielded high-quality MRI images of EH in patients with MD using a novel 7-min protocol and simplified the clinical application.Intratympanic administration of Gd-DTPA plus dexamethasone might be used to test its therapeutic effect in future work.

ELECTROACUPUNCTURE TREATMENT OF MENIERE'S DISEASE

Objective: To observe the effect of electroacupuncture (EA) on Meniere's disease. Methods: A total of 114 cases (38 males and 76 females) of Meniere's disease were treated with EA of Ermen(耳门 TE 21), Tinggong (听宫 SI 19), Tinghui (听会 GB 2), Yifeng (医风 TE 17), Fengchi (风池 GB 20) and Baihui (百会 GV 20). The treatment was given 3 times a week,9 times altogether. Follow-up was made at the end of the 3rd, 6th and 12th months after treatment. Results; Follow-up in 114 patients showed that after EA treatment, 63 cases (55.26%) were cured, 30 (26.31%) had remarkable improvement in their symptoms, 10 (8. 77%) responded with improvement and 11 (9.65%) failed in the treatment, with a total effective rate of 90.35%. Conclusion: EA treatment was effective in controlling Meniere's disease patients' symptoms and reducing attack.

MEFV,IRF8,ADA,PEPD,and NBAS gene variants and elevated serum cytokines in a patient with unilateral sporadic Meniere's disease and vascular congestion over the endolymphatic sac

The etiology and underlying mechanism of Meniere's disease(MD)development are still unknown,although inflammation and autoimmunity have been implicated as underlying mechanisms.The human endolymphatic sac(ES)has been reported to have innate and adaptive immune capacity in local immune reactions.In vivo demonstration of inflammation of the ES in patients with MD is missing in the literature.We report the case of a 47-year-old female patient diagnosed with unilateral MD with genetic variants and cytokine markers indicating inflammation and vascular congestion of the ES.Endolymphatic hydrops in the right cochlea(grade 2)and vestibulum(grade 3)were detected using MRI.She carried heterozygous variants in MEFV(c.442G>C),IRF8(c.1157G>T),ADA(c.445C>T),PEPD(c.151G>A),NBAS(c.4049T>C),CSF2RB(c.2222C>T),HPS6(c.277G>T),IL2RB(c.1109C>T),IL12RB1(c.1384G>T),IL17RC(c.260_271del GCAAGAGC TGGG),LIG1(c.746G>A),RAG1(c.650C>A),and SLX4(c.1258G>C,c.5072A>G).In the serum,the levels of granulocyte colony-stimulating factor(G-CSF),macrophage inflammatory protein 1a,and IL7 were significantly elevated,and the level of IL2Ra was reduced.Intratympanic administration of dexamethasone temporarily alleviated her hearing loss.Her vertigo was significantly relieved but remained slight after ES administration of corticosteroids.

Study on medication rules of traditional Chinese medicine for Meniere's disease based on data analysis

Objective:Study on medication rules of traditional Chinese medicine in treating Meniere's disease based on data mining technology.Methods:Computer retrieval with since establishment of the“CNKI”,“WF”,“VIP”,there have been literatures on the treatment of Meniere syndrome with Traditional Chinses medicine.Memory preprocessing in accordance with inclusion criteria.Then,EXCLE 2010,SPSS Statistics(ver.25)and SPSS Modeler(ver.18.0)were adopted respectively for frequency analysis,cluster analysis and association rules analysis.Result:A total of 133 references were included in this study,146 prescriptions,192 kinds of drugs,and the total frequency of drugs was 1702.The high frequency Meniere syndrome types were spleen deficiency and phlegm dampness syndrome,wind phlegm syndrome,gallbladder depression and phlegm disturbance syndrome,hyperactivity of liver yang syndrome,phlegm and blood stasis syndrome.The efficacy of drug frequency≥25 were summarized as follows,antiasthmatic drugs for relieving phlegm and relieving cough,diuresis-removing dampness,Tonic drugs,etc.High frequency meridian of drugs are:lung,liver,spleen,etc.High frequency drug properties are:temperature,cold,flat etc.High frequency drug taste:bitter,sweet,pungent,etc.Core drugs:Pinellia,Atractylodes,Poria,Gastrodia,etc.The main prescriptions werealisma soup,Banxia Baizhu Tianma Decoction,Zhengan Xifeng Decoction and Xiaochaihu Decoction.Conclusion:In this study,data mining was used to sort out the treatment of Meniere's disease by traditional Chinese medicine.It was found that the treatment of Meniere's disease was mainly to calm the liver and strengthen the spleen,supplemented by regulating qi and activating blood,clearing heat and opening orifices,tonifying deficiency and tranquilizing mind.

Correlation of semi-quantitative findings of endolymphatic hydrops in MRI with the audiometric findings in patients with Meniere's disease

Purpose:To investigate the correlation between vestibular hydrops(VH),cochlearhydrops(CH),vestibular aqueduct non-visibility(VANV),and visually increased perilymphatic enhancement(VIPE)with the findings of pure-tone audiometry(PTA)in Meniere’s disease(MD)patients.Methods:In this cross-sectional study,53 ears belonging to 48 patients were divided into two groups and evaluated.In group“MD patients,”there were 24 ears of 19 patients diagnosed with the definite MD(14 patients with unilateral and 5 patients withbilateral involvements).The“control group”consisted of 29 non-symptomatic ears belonging to patients diagnosed with unilateral sudden sensory-neural hearing loss or unilateral schwannoma.All the patients underwent 2 sessions of temporal bone MRI using the same 3T system:an unenhanced axial T1,T2,and 3D-FLAIR MRI,an intravenous gadoliniumenhanced axial T1 fat-sat,and 4 h after the injection,an axial 3D-T2 cube and 3D-FLAIR session.VH,CH,VANV,and VIPE were assessed.Subsequently,the correlation between EH indices and PTA findings(in three frequency domains of low,middle,and high)were evaluated,and the predictive value of MRI was calculated.Results:VH was significantly correlated with the hearing threshold in the low,middle,and highfrequency domains.CH was also correlated with the hearing threshold in the low and middle domains.Contrarily,VIPE was not associated with hearing thresholds,and VANV was only correlated with the hearing threshold in low frequencies.Conclusion:The grade of VH,CH,and VANV were significantly correlated with the hearing thresholds in PTA.

The role of selective serotonin reuptake inhibitors and tricyclic antidepressants in addressing reduction of Meniere's disease burden:A scoping review

Objective:To assess the effect of selective serotonin reuptake inhibitors(SSRIs)and tricyclic antidepressants(TCAs)in reducing vertigo,tinnitus,and hearing loss among patients with Meniere's disease(MD).Data Sources:The following databases were utilized in this scoping review:Ovid Medline,PubMed-NCBI,CINAHL,Cochrane Library,Web of Science,and Clinicaltrials.gov.Method:Studies were identified through the following search phrases:"serotonin specific reuptake inhibitors"OR"tricyclic antidepressants"AND"Meniere's disease."References from included manuscripts were examined for possible inclusion of additional studies.Results:The literature search yielded 23 results,which were screened by three independent reviewers.Seventeen studies and three duplicates were excluded.An examination of references from the included studies yielded two additional publications.A total of four published studies assessing SSRIs and TCAs among 147 patients with MD were ultimately included.Four studies described significant reductions in vertigo attack frequency among patients treated with either SSRIs or TCAs compared to their pretreatment baseline.Three studies assessed the drugs'effects on hearing,of which none found a significant difference among patients treated with SSRIs or TCAs.One study found a significant decrease in patient-reported tinnitus following treatment with TCAs or SSRIs compared to their pretreatment baseline.Conclusions:Data exploring SSRIs and TCAs among patients with MD suggests that these medications may reduce the frequency of tinnitus and vertigo,although there was significant heterogeneity in outcome reporting.There remains a need for larger-scale prospective studies that emphasize objective data to evaluate their effective-ness in reducing common MD symptoms.

Endolymphatic hydrops in Meniere's disease secondary to otitis media and visualized by gadolinium-enhanced magnetic resonance imaging

Aimed to test the hypothesis that endolymphatic hydrops in Meniere's disease(MD) may be secondary to otitis media, history of a patient who developed MD as a complication of otitis media was reviewed. The inner ear was imaged using a 3.0 Tesla MR system post-intravenous injection of gadolinium-tetraazacyclododecane-tetraacetic acid(Gd-DOTA) in a standard single dosage(0.1 mmol/kg). Both t2-spc-rst-tra-iso(T2-weighted) and heavily T2-weighted 3-dimensional fluid-attenuated inversion recovery magnetic resonance imaging [h T(2)W-3D-FLAIR] sequences were applied. As a result, in the T2-weighted images, the perilymph and endolymph, cerebrospinal fluid surrounding the eighth nerve(N8), and middle ear granulation tissue showed intense signals. In the h T(2)W-3D-FLAIR images, evident enhancement by Gd-DOTA was observed in the middle ear cavity and the perilymphatic compartments of the cochlea. Cochlear endolymphatic hydrops was implicated by the enlarged scala media in the basalturn. In general, the Gd-DOTA uptake in the vestibule was weak, and signs of vestibular endolymphatic hydrops were obvious. The N8 on the diseased side was also significantly enhanced. To conclude, endolymphatic hydrops in MD may be induced by otitis media. Cochlear endolymphatic hydrops in MD secondary to otitis media may not follow the classical pattern.

Microglial response to aging and neuroinflammation in the development of neurodegenerative diseases

Cellular senescence and chronic inflammation in response to aging are considered to be indicators of brain aging;they have a great impact on the aging process and are the main risk factors for neurodegeneration.Reviewing the microglial response to aging and neuroinflammation in neurodegenerative diseases will help understand the importance of microglia in neurodegenerative diseases.This review describes the origin and function of microglia and focuses on the role of different states of the microglial response to aging and chronic inflammation on the occurrence and development of neurodegenerative diseases,including Alzheimer's disease,Huntington's chorea,and Parkinson's disease.This review also describes the potential benefits of treating neurodegenerative diseases by modulating changes in microglial states.Therefore,inducing a shift from the neurotoxic to neuroprotective microglial state in neurodegenerative diseases induced by aging and chronic inflammation holds promise for the treatment of neurodegenerative diseases in the future.

The role of exosomes in adult neurogenesis:implications for neurodegenerative diseases

Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exosomes exert biological function by transporting factors between different cells and by regulating biological pathways in recipient cells.As an important form of intercellular communication,exosomes are increasingly being investigated due to their ability to transfer bioactive molecules such as lipids,proteins,mRNAs,and microRNAs between cells,and because they can regulate physiological and pathological processes in the central nervous system.Adult neurogenesis is a multistage process by which new neurons are generated and migrate to be integrated into existing neuronal circuits.In the adult brain,neurogenesis is mainly localized in two specialized niches:the subventricular zone adjacent to the lateral ventricles and the subgranular zone of the dentate gyrus.An increasing body of evidence indicates that adult neurogenesis is tightly controlled by environmental conditions with the niches.In recent studies,exosomes released from different sources of cells were shown to play an active role in regulating neurogenesis both in vitro and in vivo,thereby participating in the progression of neurodegenerative disorders in patients and in various disease models.Here,we provide a state-of-the-art synopsis of existing research that aimed to identify the diverse components of exosome cargoes and elucidate the therapeutic potential of exosomal contents in the regulation of neurogenesis in several neurodegenerative diseases.We emphasize that exosomal cargoes could serve as a potential biomarker to monitor functional neurogenesis in adults.In addition,exosomes can also be considered as a novel therapeutic approach to treat various neurodegenerative disorders by improving endogenous neurogenesis to mitigate neuronal loss in the central nervous system.

Unraveling the gut-brain axis:the impact of steroid hormones and nutrition on Parkinson's disease

This comprehensive review explores the intricate relationship between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the context of the gut-brain axis.The gut-brain axis plays a pivotal role in neurodegenerative diseases like Parkinson's disease,encompassing diverse components such as the gut microbiota,immune system,metabolism,and neural pathways.The gut microbiome,profoundly influenced by dietary factors,emerges as a key player.Nutrition during the first 1000 days of life shapes the gut microbiota composition,influencing immune responses and impacting both child development and adult health.High-fat,high-sugar diets can disrupt this delicate balance,contributing to inflammation and immune dysfunction.Exploring nutritional strategies,the Mediterranean diet's anti-inflammatory and antioxidant properties show promise in reducing Parkinson's disease risk.Microbiome-targeted dietary approaches and the ketogenic diet hold the potential in improving brain disorders.Beyond nutrition,emerging research uncovers potential interactions between steroid hormones,nutrition,and Parkinson's disease.Progesterone,with its anti-inflammatory properties and presence in the nervous system,offers a novel option for Parkinson's disease therapy.Its ability to enhance neuroprotection within the enteric nervous system presents exciting prospects.The review addresses the hypothesis thatα-synuclein aggregates originate from the gut and may enter the brain via the vagus nerve.Gastrointestinal symptoms preceding motor symptoms support this hypothesis.Dysfunctional gut-brain signaling during gut dysbiosis contributes to inflammation and neurotransmitter imbalances,emphasizing the potential of microbiota-based interventions.In summary,this review uncovers the complex web of interactions between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the gut-brain axis framework.Understanding these connections not only offers novel therapeutic insights but also illuminates the origins of neurodegenerative diseases such as Parkinson's disease.

Amyloid-beta and tau protein beyond Alzheimer's disease

The aggregation of amyloid-beta peptide and tau protein dysregulation are implicated to play key roles in Alzheimer's disease pathogenesis and are considered the main pathological hallmarks of this devastating disease.Physiologically,these two proteins are produced and expressed within the normal human body.However,under pathological conditions,abnormal expression,posttranslational modifications,conformational changes,and truncation can make these proteins prone to aggregation,triggering specific disease-related cascades.Recent studies have indicated associations between aberrant behavior of amyloid-beta and tau proteins and various neurological diseases,such as Alzheimer's disease,Parkinson's disease,and amyotrophic lateral sclerosis,as well as retinal neurodegenerative diseases like Glaucoma and age-related macular degeneration.Additionally,these proteins have been linked to cardiovascular disease,cancer,traumatic brain injury,and diabetes,which are all leading causes of morbidity and mortality.In this comprehensive review,we provide an overview of the connections between amyloid-beta and tau proteins and a spectrum of disorders.

Lactate metabolism in neurodegenerative diseases

Lactate,a byproduct of glycolysis,was thought to be a metabolic waste until the discovery of the Warburg effect.Lactate not only functions as a metabolic substrate to provide energy but can also function as a signaling molecule to modulate cellular functions under pathophysiological conditions.The Astrocyte-Neuron Lactate Shuttle has cla rified that lactate plays a pivotal role in the central nervous system.Moreover,protein lactylation highlights the novel role of lactate in regulating transcription,cellular functions,and disease development.This review summarizes the recent advances in lactate metabolism and its role in neurodegenerative diseases,thus providing optimal pers pectives for future research.

Muscle strength and non-alcoholic fatty liver disease/metabolicassociated fatty liver disease

This editorial comments on an article published in a recent issue of World Journal of Gastroenterology,entitled“Association of low muscle strength with metabolic dysfunction-associated fatty liver disease:A nationwide study”.We focused on the association between muscle strength and the incidence of non-alcoholic fatty liver disease(NAFLD)and metabolic-associated fatty liver disease(MAFLD),as well as the mechanisms underlying the correlation and related clinical applications.NAFLD,which is now redefined as MAFLD,is one of the most common chronic liver diseases globally with an increasing prevalence and is characterized by malnutrition,which may contribute to decreased muscle strength.Reduction of muscle strength reportedly has a pathogenesis similar to that of NAFLD/MAFLD,including insulin resistance,inflammation,sedentary behavior,as well as insufficient vitamin D.Multiple studies have focused on the relationship between sarcopenia or muscle strength and NAFLD.However,studies investigating the relationship between muscle strength and MAFLD are limited.Owing to the shortage of specific medications for NAFLD/MAFLD treatment,early detection is essential.Furthermore,the relationship between muscle strength and NAFLD/MAFLD suggests that improvements in muscle strength may have an impact on disease prevention and may provide novel insights into treatments including dietary therapy,as well as tailored physical activity.

Neuroprotective effects of chaperone-mediated autophagy in neurodegenerative diseases

Chaperone-mediated autophagy is one of three types of autophagy and is characterized by the selective degradation of proteins.Chaperone-mediated autophagy contributes to energy balance and helps maintain cellular homeostasis,while providing nutrients and support for cell survival.Chaperone-mediated autophagy activity can be detected in almost all cells,including neurons.Owing to the extreme sensitivity of neurons to their environmental changes,maintaining neuronal homeostasis is critical for neuronal growth and survival.Chaperone-mediated autophagy dysfunction is closely related to central nervous system diseases.It has been shown that neuronal damage and cell death are accompanied by chaperone-mediated autophagy dysfunction.Under certain conditions,regulation of chaperone-mediated autophagy activity attenuates neurotoxicity.In this paper,we review the changes in chaperone-mediated autophagy in neurodegenerative diseases,brain injury,glioma,and autoimmune diseases.We also summarize the most recent research progress on chaperone-mediated autophagy regulation and discuss the potential of chaperone-mediated autophagy as a therapeutic target for central nervous system diseases.

Mitophagy in neurodegenerative disease pathogenesis

Mitochondria are critical cellular energy resources and are central to the life of the neuron.Mitophagy selectively clears damaged or dysfunctional mitochondria through autophagic machinery to maintain mitochondrial quality control and homeostasis.Mature neurons are postmitotic and consume substantial energy,thus require highly efficient mitophagy pathways to turn over damaged or dysfunctional mitochondria.Recent evidence indicates that mitophagy is pivotal to the pathogenesis of neurological diseases.However,more work is needed to study mitophagy pathway components as potential therapeutic targets.In this review,we briefly discuss the characteristics of nonselective autophagy and selective autophagy,including ERphagy,aggrephagy,and mitophagy.We then introduce the mechanisms of Parkin-dependent and Parkin-independent mitophagy pathways under physiological conditions.Next,we summarize the diverse repertoire of mitochondrial membrane receptors and phospholipids that mediate mitophagy.Importantly,we review the critical role of mitophagy in the pathogenesis of neurodegenerative diseases including Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis.Last,we discuss recent studies considering mitophagy as a potential therapeutic target for treating neurodegenerative diseases.Together,our review may provide novel views to better understand the roles of mitophagy in neurodegenerative disease pathogenesis.

SIRT2 as a potential new therapeutic target for Alzheimer's disease

Alzheimer's disease is the most common cause of dementia globally with an increasing incidence over the years,bringing a heavy burden to individuals and society due to the lack of an effective treatment.In this context,sirtuin 2,the sirtuin with the highest expression in the brain,has emerged as a potential therapeutic target for neurodegenerative diseases.This review summarizes and discusses the complex roles of sirtuin 2 in different molecular mechanisms involved in Alzheimer's disease such as amyloid and tau pathology,microtubule stability,neuroinflammation,myelin formation,autophagy,and oxidative stress.The role of sirtuin 2 in all these processes highlights its potential implication in the etiology and development of Alzheimer's disease.However,its presence in different cell types and its enormous variety of substrates leads to apparently contra dictory conclusions when it comes to understanding its specific functions.Further studies in sirtuin 2 research with selective sirtuin2 modulators targeting specific sirtuin 2 substrates are necessary to clarify its specific functions under different conditions and to validate it as a novel pharmacological target.This will contribute to the development of new treatment strategies,not only for Alzheimer's disease but also for other neurodegenerative diseases.