ATP-binding cassette transporters as possible targets for the intervention of neurodegenerative diseases

ATP-binding cassette(ABC)transporters are ubiquitous membrane-bound proteins that are responsible for the translocation of a broad spectrum of substrates across cellular membranes,including lipids,amino acids,nucleosides,sugars,and xenobiotics.Interestingly,ABC transporters are highly expressed in the brain.While their functions in the brain still need to be elucidated,several members are implicated in the pathogenesis of neurodegenerative diseases,including Alzheimer’s disease(AD),Parkinson’s disease(PD),and frontotemporal dementia.In this perspective,we will review current knowledge of ABC transporters in the central nervous system in terms of physiological functions and pathology in neurodegeneration.Furthermore,we will explore the possibilities of ABC transporters as potential targets in the development of therapeutics for neurodegenerative diseases.

Inducing neuronal regeneration and differentiation via the BDNF/ TrkB signaling pathway: a key target against neurodegenerative diseases?

Brain-derived neurotrophic factor(BDNF)is one of the neurotrophins,a specific polypeptide growth factor,which plays a crucial role in the proliferation,differentiation,survival,and death of neurons and non-neuronal cells.It is not only essential to maintain the balance between death on one side and survival of neurons on the other,but also it mediates additional higher-order activities such as learning,memory,and behavior.It is initially synthesized as a precursor protein,proBDNF,that can be secreted as it is or it can be cleaved intracellularly by furin and proconvertases,or extracellularly by extracellular proteases such as matrix metalloprotease-9 and matrix metalloprotease-2,or plasmin to give mature BDNF.

Current controversies in glia-to-neuron conversion therapy in neurodegenerative diseases

Loss of neurons and disruption of neural circuits are associated with many neurological diseases,including neurodegenerative diseases and mental disorders.The most prevalent pathological feature of neurodegenerative diseases is the aggregate loss of certain neuronal populations.For example,the loss of dopamine(DA)neurons in the substantia nigra pars compacta has been defined as a pathological hallmark of Parkinson’s disease(PD;Kamath et al.,2022).

Advances in non-invasive imaging of proteinopathies in animal models of neurodegenerative diseases

Neurodegenerative diseases,including Alzheimer's disease(AD),frontotemporal dementia,Parkinson's disease,and dementia with Lewy bodies,represent tremendous unmet clinical needs.A common feature of these diseases is the aberrant cerebral accumulation of pathological protein aggregates,affecting selectively vulnerable circuits in a disease-specific pattern.Earlier studies have established a relationship between abnormal aggregation and neuronal dysfunction or loss,suggesting multifactorial pathogenesis mechanisms in these neurodegenerative disorders.

Mitochondrial therapeutics and mitochondrial transfer for neurodegenerative diseases and aging

Mitochondrial dysfunction and neurodegeneration:Progressive neurodegenerative diseases affect a significant proportion of the population;in a single year,there are as many as 276 million disabilities and 9 million deaths as a result of neurological diseases.

Microglial dysfunction and genetic risk for neurodegenerative disease

Neurodegenerative disorders such as Alzheimer's and Parkinson's diseases a re increasing in prevalence as world populations age.While tremendous progress has been made,our understanding of the mechanisms that underlie the development of these diseases remains far from com plete.More troubling,despite the growing emotional and financial toll being to ken by neurodegenerative disorders,existing treatment options are limited almost exclusively to those that help manage symptoms but that lack the ability to alter the progression of the disease(Liu et al.,2022).

Targeting glial metabolism in neurodegenerative diseases:detail matters

Neurodegenerative diseases,a group of disorders associated with advanced age,are typified by the disease-specific accumulation of mutant proteins and neuroinflammation.For decades,treatment modalities for these disorders have focused on addressing neuronal malfu nction,which has resulted in the failure of therapies.Recent studies have identified the crucial role of glial cells in exacerbating neurodegenerative processes via the release of neuroinflammatory mediators.Glia,the major immune component of the central nervous system (CNS),undergo numerous phenotypic transitions and regulate the outcomes of various pathologies (Afridi et al.,2022).

Endplate role in the degenerative disc disease:A brief review

The degenerative disease of the intervertebral disc is nowadays an important health problem,which has still not been understood and solved adequately.The vertebral endplate is regarded as one of the vital elements in the structure of the intervertebral disc.Its constituent cells,the chondrocytes in the endplate,may also be involved in the process of the intervertebral disc degeneration and their role is central both under physiological and pathological conditions.They main functions include a role in homeostasis of the extracellular environment of the intervertebral disc,metabolic support and nutrition of the discal nucleus and annulus beneath and the preservation of the extracellular matrix.Therefore,it is understandable that the cells in the endplate have been in the centre of research from several viewpoints,such as development,degeneration and growth,reparation and remodelling,as well as treatment strategies.In this article,we briefly review the importance of vertebral endplate,which are often overlooked,in the intervertebral disc degeneration.

Role of the NLRP3 inflammasome in neurodegenerative diseases and therapeutic implications

Neurodegenerative diseases are a group of neuronal disorders caused by progressive neuronal cell death in different regions of the human brain.Alzheimer's disease(AD)and Parkinson's disease(PD)are the most common types of neurodegenerative diseases that affect millions of people worldwide.There is no cure available for either disease.One of the pathological hallmarks of neurodegenerative diseases is the abnormal protein aggregation in the central nervous system.

Is Dynesys dynamic stabilization system superior to posterior lumbar fusion in the treatment of lumbar degenerative diseases?

Dynesys,a pedicle-based dynamic stabilization system,was introduced to overcome some undesirable complications of fusion procedures.Nevertheless,the theoretical advantages of Dynesys over fusion have not been clearly confirmed.The purpose of this editorial was to compare clinical and radiological outcomes of patients who underwent Dynesys system with those who underwent posterior lumbar fusion according to the existing literature and to see if the application of the Dynesys system is superior to the traditional lumbar fusion surgery.According to published clinical reports,the short-term effects of the Dynesys dynamic stabilization system are similar to that of traditional lumbar fusion surgery.Three comparative studies of Dynesys dynamic stabilization and fusion surgery with medium-term follow-up are encouraging.However,the results from four single-treatment-arm and small-sample studies of case series with long-term follow-up were not encouraging.In the present circumstances,it is not possible to conclude that the Dynesys dynamic stabilization system is superior to fusion surgery for lumbar degenerative diseases.

Neuroprotective therapy for retinal neurodegenerative diseases by stem cell secretome

Retinal neurodegenerative diseases like agerelated macular degeneration,glaucoma,diabetic retinopathy or retinitis pigmentosa are the most frequent causes of incurable low vision and blindness worldwide.It had been estimated that the prevalence of these diseases varies between 1/750 and 1/5000 depending on the region,the level of consanguinity or ethnicity(Na et al.,2017).The functional and structural complexity of the retina makes it susceptible to multiple types of pathogenic damage.

Free ubiquitin: a novel therapeutic target for neurodegenerative diseases

Neurodegenerative diseases are widespread and the increasing number of patients with these diseases can no longer be ignored. Dementia is a symptom of many neurodegenerative diseases, and Alzheimer's disease(AD), which is associated with memory and learning disabilities, accounts for approximately 60 to 80% of all dementia cases(Wyss-Coray, 2016).

Abscisic acid, a promising therapeutic molecule to prevent Alzheimer’s and neurodegenerative diseases

Neuroinflammatory processes induce neuronal damage and underlie the onset of neurodegenerative pathologies,including Alzheimer’s disease(AD)(Calsolaro and Edison,2016).Several conditions,ranging from emotional stress to metabolic syndrome,including traumatic brain injury,chronic infections or gut microbiota disruption can cause or aggravate neuroinflammation.Moreover,aging is the major factor associated with neurodegenerative diseases.

Potential contribution of pedicle screw design to loosening rate in patients with degenerative diseases of the lumbar spine:An observational study

BACKGROUND The majority of published data report the results of biomechanical tests of various design pedicle screw performance.The clinical relevance and relative contribution of screw design to instrumentation stability have been insufficiently studied.AIM To estimate the contribution of screw design to rate of pedicle screw loosening in patients with degenerative diseases of the lumbar spine.METHODS This study is a prospective evaluation of 175 patients with degenerative diseases and instability of the lumbar spine segments.Participants underwent spinal instrumentation employing pedicle screws with posterior only or transforaminal interbody fusion.Follow-up was for 18 mo.Patients with signs of pedicle screw loosening on computed tomography were registered;logistic regression analysis was used to identify the factors that influenced the rate of loosening.RESULTS Parameters included in the analysis were screw geometry,type of thread,external and internal screw diameter and helical pitch,bone density in Hounsfield units,number of levels fused,instrumentation without anterior support,laminectomy,and unilateral and bilateral total facet joint resection.The rate of screw loosening decreased with the increment in outer diameter,decrease in core diameter and helical pitch.The rate of screw loosening correlated positively with the number of fused levels and decreasing bone density.Bilateral facet joint removal significantly favored pedicle screw loosening.The influence of other factors was insignificant.CONCLUSION Screw parameters had a significant impact on the loosening rate along with bone quality characteristics,the number of levels fused and the extensiveness of decompression.The significance of the influence of screw parameters was comparable to those of patient-and surgery-related factors.Pedicle screw loosening was influenced by helical pitch,inner and outer diameter,but screw geometry and thread type were insignificant factors.

Staining neurons with Golgi techniques in degenerative diseases ofthe brain

A detailed morphological study of neurons in healthy and pathological conditions requires reasonably a number of special techniques, which may visualize the majority of neu- rons in a thick three-dimensional arrangement. A detailed visualization of neurons must include the cell body, most of the dendritic arbor, the dendritic spines, the axon, the axonal collaterals and the synapses. An ideal morphological technique for the study of degeneration and regeneration processes of the central nervous system must also visualize clearly the long and short neuronal circuits, as well as the dendritic and axonal bands and tracks.

Management of Post-Traumatic Stress (PTSD) Dementia and Other Neuro-Degenerative Disease with Photo-Medicine: Clinical Experience and Case Studies

Objective: Photobiomodulation (also known as Low Level Laser. LLLT or Cold Laser;Photo Medicine (PM)) has been a vital adjunct therapy in our clinical practice over 5 years, observations of improvement in cognition and personality were noted in several patients. As a result, selected patients with Alzheimer’s Disease, vascular dementia, post-traumatic brain injury and other neuro-degenerative diseases were treated at clinical practices in Buffalo, New York;Sarasota, Florida;Lafayette, Indiana;Phoenix, Az., and Baton Rouge, La. Over 60 patients were treated with an average of 4 times over an 8-day period all reported/exhibited improvement in their condition, except that two men who were in their seventies were in robust health but had no short-term memory and no improvement was observed. However, Theralase has developed a more efficacious system which will be more efficacious, due to increased power for ATP activation. Method: Over 150 patients with the above conditions were treated in various areas (depending on diagnosis) including the prefrontal cortex, temporal lobe, Hippocampus, and Circle of Willis for duration of two and one-half minutes every 48 hours for 5 - 6 treatments. We utilized the Theralase multi-probe (905 nm/660 nm) at 60 miliwatts. It utilizes 5 - 905 nm near infra-red diodes and 4 infra-red 660 laser diodes with a peak power of 50,000 milliwatts at peak and pulse duration of 200 nanoseconds [1]. The PTSD patients were evaluated utilizing the co-occurring disorders program screening and assessment form. Conclusion: Dementia patients exhibited varying degrees of improvement in cognitive function and personality, leading to improved quality of life and decreased caregiver burden. PTSD patients’ improvement was objectively measured by formal neuropsychological testing utilizing the form. All PTSD patients scored no emotional problems after 3 - 5 treatments and all experienced overall sense of well-being. One experienced return of ability to smell he had not had for 5 years. Similar results were reported in a Japanese study where 15 patients were followed for a year. This non-invasive and non-systemic modality of therapy could play a key role in treating progressive neurodegenerative conditions, improving quality of life, and reducing health care costs.

Current and future therapeutic strategies for the treatment of retinal neurodegenerative diseases

The complex and mostly multiple and unknown aetiology of neurodegenerative diseases always give way to an intricate scenario of dying tissue that involves multiple cell mediators and cell types.All neurodegenerative diseases of the central nervous system(CNS)share common mechanisms,regardless their origin:oxidative stress,neuroinflammation and cell death.Accordingly,retinal degenerative diseases,with or without a genetic cause,as retinitis pigmentosa(RP),glaucoma,agerelated macular degeneration(AMD)or diabetic retinopathy(DR)do not differ in their basic mechanisms of cell death neither one to another,nor from those observed in other CNS diseases as Parkinson’s or Alzheimer’s(Cuenca et al.,2014).Indeed,the therapeutic findings should be able to be more or less easily extrapolated between these conditions,as far as they are directed to common dartboards.

Advance in the use of gold nanoparticles in the treatment of neurodegenerative diseases:new perspectives

Various conditions affecting nerve cells and the nervous system due to the loss of neurons and their connecting networks are described under the superordinate phrase“Neurodegenerative diseases”.Such diseases lead to disability due to gradual neuronal death in both the central nervous system and the peripheral nervous system.While many of these diseases have unknown causes,sometimes these are due to medical conditions such as alcoholism,a tumor,or a stroke,or other causes which may include genetic mutations,toxins,chemicals,and viruses.

Significance of intercellular communication for neurodegenerative diseases

The nervous system is a highly complex organization composed of its basicunit,the neuronal cells,and specialized supporting cells,the glial cells.The main glial cells in the central nervous system(CNS)are astrocytes,microglia and oligodendrocytes.Astrocytes are the most abundant glial cell type in the CNS.

Abnormal metal homeostasis as a common drug target to combat neurodegenerative diseases

As life expectancy increases,the prevalence of age-related diseases will also increase.There has been an estimation that 50 million individuals are living with dementia in 2019.This number will increase to 75 million in 2030 and 131.5 million by 2050(McGill-Carter,2020).Neurodegenerative diseases such as Alzheimer’s disease(AD),Parkinson´s disease(PD)and Huntington disease(HD)disproportionately affect older adult populations,inflicting a considerable physical,emotional,and economic burden.