Immunoassay development guidelines for neurodegenerative disorders:lessons from a failed pS129-α-synuclein electrochemiluminescence immunoassay

An aging population is a double-edged sword.On one hand,advancements in biotechnology and healthcare allow more people to enjoy longer lives.On the other hand,increases in the aging population accompany a surge in age-associated diseases,particularly neurodegenerative disorders.Since aging is the primary risk factor for many neurodegenerative disorders,living longer does not necessarily equate to maintaining a reasonable quality of life(Feigin et al.,2020).

Role of resident memory T cells in neuroinflammatory and neurodegenerative diseases in the central nervous system

The immune system has been attracting increasing attention in the field of chronic neurological disorders in the central nervous system(CNS).Autoreactive T cells targeting CNS antigens play a crucial role in the development of various autoimmune diseases,such as multiple sclerosis(MS)and neuromyelitis optica spectrum disorder(NMOSD).Moreover,T cells are now recognized as a pivotal contributor to the pathology of neurodegenerative disorders,including Alzheimer's disease(AD),Parkinson's disease(PD),and multiple system atrophy.

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).

Peripheral blood RNA biomarkers can predict lesion severity in degenerative cervical myelopathy

Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical myelopathy.This study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic characteristics.Enrichment analysis identified 128 differentially expressed genes that were enriched in patients with neurological disabilities.Using least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,respectively.Signatures of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%accuracy.Our results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.

Internal limiting membrane peeling combined with silicone oil or air tamponade for highly myopic foveoschisis

AIM:To compare the efficacy of pars plana vitrectomy(PPV)combined with internal limiting membrane(ILM)and silicone oil or sterile air tamponade for the treatment of myopic foveoschisis(MF)in highly myopic eyes.METHODS:This retrospective study included 48 myopic eyes of 40 patients with MF and axial lengths(ALs)ranging from 26-32 mm treated between January 2020 and January 2022.All patients were underwent PPV combined with ILM peeling followed by sterile air or silicone oil tamponade and followed up at least 12mo.Based on the features on spectral-domain optical coherence tomography(SD-OCT),the eyes were divided into the MF-only group(Group A,n=15 eyes),MF with central foveal detachment group(Group B,n=20 eyes),and MF with lamellar macular hole group(Group C,n=13 eyes).According to AL,eyes were further divided into three groups:Group D(26.01-28.00 mm,n=12 eyes),Group E(28.01-30.00 mm,n=26 eyes),and Group F(30.01-32.00 mm,n=10 eyes).The best-corrected visual acuity(BCVA),central foveal thickness(CFT),and complications were recorded.RESULTS:The patients included 16 males and 24 females with the mean age of 56±9.82y.The BCVA and CFT improved in all groups after surgery(P<0.01),while there was no significant difference of the CFT in Group A,B,and C postoperatively(P>0.05).The intergroup differences of BCVA and CFT postoperatively were statistically significant in Group D,E,and F.Twenty eyes were injected with sterile air,and 28 eyes were injected with silicone oil for tamponade based on the AL.However,there was no statistically significant difference among Groups D,E,and F in terms of the results of sterile air or silicone oil tamponade.The mean recovery time was 5.9mo for MF patients subjected to silicone oil tamponade and 7.7mo for patients subjected to sterile air tamponade,and the difference was not statistically significant.CONCLUSION:PPV and ILM peeling combined with silicone oil or sterile air tamponade can achieve good results for MF in highly myopic eyes with ALs≤32 mm.

Using choroidal thickness to detect myopic macular degeneration

AIM:To explore the usage of choroidal thickness measured by swept-source optical coherence tomography(SS-OCT)to detect myopic macular degeneration(MMD)in high myopic participants.METHODS:Participants with bilateral high myopia(≤−6 diopters)were recruited from a subset of the Guangzhou Zhongshan Ophthalmic Center-Brien Holden Vision Institute High Myopia Cohort Study.SS-OCT was performed to determine the choroidal thickness,and myopic maculopathy was graded by the International Meta-Analysis for Pathologic Myopia(META-PM)Classification.Presence of MMD was defined as META-PM category 2 or above.RESULTS:A total of 568 right eyes were included for analysis.Eyes with MMD(n=106,18.7%)were found to have older age,longer axial lengths(AL),higher myopic spherical equivalents(SE),and reduced choroidal thickness in each Early Treatment Diabetic Retinopathy Study(ETDRS)grid sector(P<0.001).The area under the receiver operating characteristic(ROC)curves(AUC)for subfoveal choroidal thickness(0.907)was greater than that of the model,including age,AL,and SE at 0.6249,0.8208,and 0.8205,respectively.The choroidal thickness of the inner and outer nasal sectors was the most accurate indicator of MMD(AUC of 0.928 and 0.923,respectively).An outer nasal sector choroidal thickness of less than 74μm demonstrated the highest odds of predicting MMD(OR=33.8).CONCLUSION:Choroidal thickness detects the presence of MMD with high agreement,particularly of the inner and outer nasal sectors of the posterior pole,which appears to be a biometric parameter more precise than age,AL,or SE.

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.

Nuance of inward rectifying potassium(Kir)channel dysfunctions in neurodegenerative diseases

Neurodegenerative disorders are highly prevalent and diverse in nature.Their manifestation largely depends on the cell types involved,with aberrant inflammatory episodes progressively inducing a constellation of phenotypes that are classified into specific diseases based on their neuropathological traits.The two most prevalent neurodegenerative diseases worldwide,Alzheimer’s disease(AD)and Parkinson’s disease(PD),for example,share notable similarities,yet they differ in terms of the specific cell types lost within the central nervous system(CNS).The significant and progressive loss of cortical and certain subcortical neurons in various regions is a major defining trait of AD.In contrast,the specific loss of dopaminergic neurons(DA)within the substantial nigra pars compacta(SNpc)is sufficient to cause motor symptoms associated with PD.Another devastating condition arising from neurodegeneration within the CNS,amyotrophic lateral sclerosis(ALS),results in the progressive death of upper and lower motor neurons.This degeneration originates in oligodendrocytes,whose defective myelination abilities lead to the denervation of the anterior horn,aggravating motor neuron death.

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.

Advancements in personalized stem cell models for aging-related neurodegenerative disorders

Neurodegenerative diseases(NDDs)are a class of disorders characterized by the gradual loss or malfunction of specific cell populations in the nervous system,which can be triggered by genetic or environmental factors.As a result,patients often experience a decline in mobility,sensation,memory,and cognition,which can ultimately lead to a fatal outcome.The global incidence of NDDs,including Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,amyotrophic lateral sclerosis(ALS),and multiple sclerosis,is increasing.

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).

Stress granules: friend or foe in neurodegenerative disorders?

Neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis,despite the diversity in clinical symptoms,share a striking feature at the cellular level:the accumulation of insoluble aggregates of misfolded proteins that are sequestered in intraneuronal inclusion bodies.Besides mutations in disease-associated proteins that render them aggregation-prone,the decline of protein homeostasis(i.e.proteostasis)with aging is also believed to be a contributing factor to the accumulation of protein aggregates.

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.

Potential role of tubulin glutamylation in neurodegenerative diseases

The differentiation of neuronal stem cells into mature neurons is a complex process that involves both structural and functional changes.As cells undergo differentiation,there are notable functional changes,including the expression of various transcription factors,cytokines,and neurotransmitiers.Additionally,structural changes occur as the cells develop various processes from the cell body and establish synaptic contacts with other cells.

Exploring the synergy of the eyebrain connection:neuromodulation approaches for neurodegenerative disorders through transcorneal electrical stimulation

The connection and interaction between the eye and the brain are crucial to understanding brain disorders(Marchesi et al.,2021).Both the eye and the brain have a limited regenerative capacity as there are few progenitor cells,and nerve cells do not replicate.Hence,neurodegeneration implicates irreversible damage to the central nervous system,as observed in several neurodegenerative diseases(Marchesi et al.,2021).

Cognition and movement in neurodegenerative disorders:a dynamic duo

People with neurodegenerative disorders often experience problems across a variety of functional domains,including cognition,movement,and psychosocial functioning.The classification of these disorders is based on the phenotypical manifestations that represent the most prominent clinical features.For example,Parkinson's disease and Huntington's disease are typically regarded as movement disorders,whereas Alzheimer's disease(AD) and other dementias are regarded as cognitive disorders.

New insights into astrocyte diversity from the lens of transcriptional regulation and their implications for neurodegenerative disease treatments

Astrocytes are a major glial cell type in the central nervous system,and they provide trophic and metabolic support to neurons.In addition to these roles,they play crucial roles in modulating synaptic functions,development,and pruning(Brandebura et al.,2023).Astrocytes become reactive(activated)by undergoing morphological,molecular,and functional alterations in response to neuropathology such as in injuries and neurodegenerative diseases(NDs)(Escartin et al.,2021).

Clinical Study of Accelerated Rehabilitation Concept Combined with Tianji Robot-Assisted Surgery in Lumbar Degenerative Diseases

Objective: To compare the effectiveness and safety of two surgical methods for lumbar degenerative diseases;the combination of the concept of accelerated rehabilitation with the assistance of Tianji Robotics and the concept of accelerated rehabilitation combined with manual pedicle screw placement assisted by conventional C-arm fluoroscopy. Methods: A retrospective analysis was performed on 70 patients who received the concept of accelerated rehabilitation combined with spinal surgery for lumbar degenerative diseases in Baise People’s Hospital from January 2022 to January 2024. Among them, 35 patients in the robot group received accelerated rehabilitation concept combined with robot-assisted surgery;In the conventional C-arm group, 35 patients received the accelerated rehabilitation concept combined with manual pedicle screw placement assisted by conventional C-arm fluoroscopy. VAS score (preoperative/postoperative), ODI score (preoperative/postoperative), intraoperative bleeding volume, postoperative hospital stay, postoperative complications and the accuracy rate of screw placement were compared between the two groups. Result: There was no statistically significant difference in preoperative VAS scores between the robot group and the conventional C-arm group (6.45 ± 0.82 VS 6.63 ± 0.81, P = 0.6600). The postoperative VAS score of the robot group was better than that of the conventional C-arm group (1.69 ± 0.80 VS 2.45 ± 0.85, P = 0.0000*). There was no statistically significant difference in preoperative ODI scores between the robot group and the conventional C-arm group (32.11 ± 3.18 VS 31.66 ± 2.25, P = 0.4900). The postoperative ODI score of the robot group was better than that of the conventional C-arm group (22.68 ± 1.94 VS 24.57 ± 2.25, P = 0.0000*). The postoperative complications in the robot group were less than those in the conventional C-arm group (2.7778% VS 28.5724%, P = 0.0030*). The intraoperative bleeding in the robot group was lower than that in the conventional C-arm group (320.85 ± 276.28 VS 490.00 ± 395.34, P = 0.0420*). The postoperative hospital stay of the robot group was shorter than that of the conventional C-arm group (10.00 ± 9.32 VS 14.49 ± 7.55, P = 0.0300*). The screw placement inaccuracy score of the robot group was lower than that of the conventional C-arm group (0.17 ± 0.51 VS 1.45 ± 1.46, P = 0.0000*). Conclusion: The combination of the concept of accelerated rehabilitation and Tianji Orthopedic robot-assisted surgery is more effective and safer in posterior lumbar decompression and internal fixation surgery with a screw rod system, and is worthy of promotion and application.

Insights into the underlying pathogenesis and therapeutic potential of endoplasmic reticulum stress in degenerative musculoskeletal diseases

Degenerative musculoskeletal diseases are structural and functional failures of the musculoskeletal system,including osteoarthritis,osteoporosis,intervertebral disc degeneration(IVDD),and sarcopenia.As the global population ages,degenerative musculoskeletal diseases are becoming more prevalent.However,the pathogenesis of degenerative musculoskeletal diseases is not fully understood.Previous studies have revealed that endoplasmic reticulum(ER)stress is a stress response that occurs when impairment of the protein folding capacity of the ER leads to the accumulation of misfolded or unfolded proteins in the ER,contributing to degenerative musculoskeletal diseases.By affecting cartilage degeneration,synovitis,meniscal lesion,subchondral bone remodeling of osteoarthritis,bone remodeling and angiogenesis of osteoporosis,nucleus pulposus degeneration,annulus fibrosus rupture,cartilaginous endplate degeneration of IVDD,and sarcopenia,ER stress is involved in the pathogenesis of degenerative musculoskeletal diseases.Preclinical studies have found that regulation of ER stress can delay the progression of multiple degenerative musculoskeletal diseases.These pilot studies provide foundations for further evaluation of the feasibility,efficacy,and safety of ER stress modulators in the treatment of musculoskeletal degenerative diseases in clinical trials.In this review,we have integrated up-to-date research findings of ER stress into the pathogenesis of degenerative musculoskeletal diseases.In a future perspective,we have also discussed possible directions of ER stress in the investigation of degenerative musculoskeletal disease,potential therapeutic strategies for degenerative musculoskeletal diseases using ER stress modulators,as well as underlying challenges and obstacles in bench-to-beside research.