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.

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.

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.

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.

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.

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).

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).

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.

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.

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.

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).

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。