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.

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.

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.

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.

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).

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.

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.

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.

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.

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).

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).

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).

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.

A perspective on causality assessment in epigenetic research on neurodegenerative disorders

Epigenetics refers to herita ble and reversible processes regulating gene expression that do not involve a change to the DNA sequence.Epigenetic modifications include DNA modifications(e.g.DNA methylation a nd hydroxymethyl at ion),histone modifications,and non-coding RNAs such as micro RNAs and long-coding RNAs(Holtzman and Gersbach.

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).

Translation stalling and ribosome collision leading to proteostasis failure:implications for neurodegenerative diseases

Proteostasis denotes a cellular state in which protein synthesis,folding,and degradation are maintained at a homeostatic state such that an intact yet dynamic proteome is preserved.Cellular capacity to preserve proteostasis declines with age,which is assumed to contribute to the pathogenesis of age-related diseases.Proteostasis failure manifested as the formation of aberrant protein aggregates,including the amyloid plaques in Alzheimer’s disease(AD),Lewy bodies in Parkinson’s disease,and TAR DNA binging protein 43 inclusions in amyotrophic lateral sclerosis(ALS),is a defining feature of neurodegenerative diseases.

Disease-associated oligodendrocyte signatures in neurodegenerative disease:the known and unknown

Oligodendrocytes are one of the most abundant cell types in the central nervous system(CNS)and act in close contact with neurons to assist with their cellular function and health(Kuhn et al.,2019).Oligodendrocytes play particular roles in rapid nerve impulse conduction through the wrapping of their myelinating projections a round a nerve axon,as well as by offering trophic and metabolic support for the high energy expenditure of neurons.Additionally。

Cell senescence,loss of splicing,and lipid metabolism in TDP-43-related neurodegenerative processes

In recent work,we have shown that cell senescence of mouse fibroblasts in vitro associates with a build-up of cryptic exons in selected mRNAs,whose level is usually controlled by the activity of TAR DNA binding protein of 43 kDa(Tdp-43)(Torres et al.,2022).In vivo,we also found traits of cell senescence in the motor neuron disease model achieved by overexpressing SOD-G93A,the SOD1 gene(harboring a single amino acid substitution of glycine to alanine at codon 93).

Hyperhomocysteinemia: Risk Factors and Faster Onset of Degenerative Complications of Type 2 Diabetes in Brazzaville

Background: Type 2 diabetes (T2D) remains a major global public health problem. This complex metabolic disorder can lead to various complications, including cardiovascular diseases (leading cause of death) in T2D. Among the biochemical markers associated with increased risk for cardiovascular disease, homocysteine is currently one of the predictive markers under evaluation. We investigate the link between hyperhomocysteinemia and diabetes complications in DT2 population in Brazzaville. Methodology: We conducted a cross-sectional analytical study, from October to December 2022. One hundred and fifty participants were included, 100 patients T2D (34 with complications, 33 with comorbidities, 33 without), and 50 patients controls. Sociodemographic and clinical characteristics were collected. Homocysteine (Hcy) serum levels were measured using Sandwich ELISA method. Results: Study population was composed of 50% males and 50% females with sex ratio of 1;mean age was 52.2 ± 10.8 years (30 - 83). The prevalence of hyperhomocysteinemia (HHcy) was 36% (20% moderate Hcy, 15% intermediate and 1% severe). Mean Hcy concentration was 31.9 μmol/l (18 - 103). Age, gender and physical inactivity were strongly correlated to Hcy (OR of 3.5;9.4 and 3 respectively). Multivariate analysis showed that HHcy was a risk accelerator for degenerative complications (stroke: OR = 6.2;ischemic heart disease: 4.9;neuropathy: 9.2;retinopathy: 4.5 and peripheral arterial disease: 4.9). Conclusion: These findings suggest that hyperhomocysteinemia can be considered as a predictive marker to be taken into account in targeting cardiovascular risk in Congolese subjects with T2D.

New horizon:microenvironment regulation in neurodegenerative diseases

Neurodegenerative disease refers to a class of diseases that cause dysfunction of the nervous system due to the death of nerve cells.These diseases are caused by the gradual death of neurons,which has a serious impact on the lives of patients.