Neurological Sciences, Год журнала: 2024, Номер 45(7), С. 3117 - 3124
Опубликована: Янв. 25, 2024
Язык: Английский
International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(21), С. 12841 - 12841
Опубликована: Окт. 25, 2022
Alzheimer’s disease (AD) is the leading cause of dementia in elderly people. Amyloid beta (Aβ) deposits and neurofibrillary tangles are major pathological features an brain. These proteins highly expressed nerve cells found most tissues. Tau primarily provides stabilization to microtubules part axons dendrites. However, tau a state becomes hyperphosphorylated, causing dysfunction synaptic impairment degeneration neurons. This article presents summary role tau, phosphorylated (p-tau) AD, other tauopathies. Tauopathies, including Pick’s disease, frontotemporal dementia, corticobasal degeneration, argyrophilic grain progressive supranuclear palsy, Huntington’s result misprocessing accumulation within neuronal glial cells. also focuses on current research post-translational modifications genetics pathology, tauopathies development new drugs targeting p-tau, therapeutics for treating possibly preventing
Язык: Английский
Процитировано
184
Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)
Опубликована: Авг. 23, 2024
Abstract Alzheimer’s disease (AD) stands as the predominant form of dementia, presenting significant and escalating global challenges. Its etiology is intricate diverse, stemming from a combination factors such aging, genetics, environment. Our current understanding AD pathologies involves various hypotheses, cholinergic, amyloid, tau protein, inflammatory, oxidative stress, metal ion, glutamate excitotoxicity, microbiota-gut-brain axis, abnormal autophagy. Nonetheless, unraveling interplay among these pathological aspects pinpointing primary initiators require further elucidation validation. In past decades, most clinical drugs have been discontinued due to limited effectiveness or adverse effects. Presently, available primarily offer symptomatic relief often accompanied by undesirable side However, recent approvals aducanumab ( 1 ) lecanemab 2 Food Drug Administration (FDA) present potential in disrease-modifying Nevertheless, long-term efficacy safety need Consequently, quest for safer more effective persists formidable pressing task. This review discusses pathogenesis, advances diagnostic biomarkers, latest updates trials, emerging technologies drug development. We highlight progress discovery selective inhibitors, dual-target allosteric modulators, covalent proteolysis-targeting chimeras (PROTACs), protein-protein interaction (PPI) modulators. goal provide insights into prospective development application novel drugs.
Язык: Английский
Процитировано
129
Biomedicine & Pharmacotherapy, Год журнала: 2022, Номер 148, С. 112681 - 112681
Опубликована: Фев. 14, 2022
Alzheimer's disease (AD) is the most common neurodegenerative disease, with cognitive decline as primary clinical feature. According to epidemiological statistics, 50 million people worldwide are currently affected by disease. Although new drugs such aducanumab have been approved for use in treatment of AD, none them reversed progression AD. MicroRNAs (miRNAs) small molecule RNAs that exert their biological functions regulating expression intracellular proteins, and differential abundance varieties found between central peripheral tissues AD patients healthy controls. This article will summarise changes miRNAs process, potential role diagnostic markers therapeutic targets be explored.
Язык: Английский
Процитировано
125
International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(7), С. 6518 - 6518
Опубликована: Март 30, 2023
Alzheimer’s disease is one of the most commonly diagnosed cases senile dementia in world. It an incurable process, often leading to death. This multifactorial, and factor this inflammation. Numerous mediators secreted by inflammatory cells can cause neuronal degeneration. Neuritis may coexist with other mechanisms disease, contributing progression, also directly underlie AD. Although much has been established about processes pathogenesis AD, many aspects remain unexplained. The work devoted particular pathomechanism inflammation its role diagnosis treatment. An in-depth detailed understanding neuroinflammation help development diagnostic methods for early contribute new therapeutic strategies disease.
Язык: Английский
Процитировано
99
Physiological Reviews, Год журнала: 2023, Номер 104(1), С. 103 - 197
Опубликована: Окт. 16, 2023
Alzheimer disease (AD) is associated with multiple etiologies and pathological mechanisms, among which oxidative stress (OS) appears as a major determinant. Intriguingly, OS arises in various pathways regulating brain functions, it seems to link different hypotheses mechanisms of AD neuropathology high fidelity. The particularly vulnerable damage, mainly because its unique lipid composition, resulting an amplified cascade redox reactions that target several cellular components/functions ultimately leading neurodegeneration. present review highlights the “OS hypothesis AD,” including amyloid beta-peptide-associated role protein oxidation unraveled by proteomics, antioxidant strategies have been investigated modulate progression AD. Collected studies from our groups others contributed unraveling close relationships between perturbation homeostasis elucidating redox-regulated events potentially involved both pathogenesis However, complexity requires in-depth understanding intracellular affecting relevant for functions. This crucial developing pharmacological targeting OS-mediated toxicity may contribute slow well improve quality life persons this severe dementing disorder.
Язык: Английский
Процитировано
71
Biomedicines, Год журнала: 2023, Номер 11(9), С. 2488 - 2488
Опубликована: Сен. 7, 2023
Mitochondria play a vital role in maintaining cellular energy homeostasis, regulating apoptosis, and controlling redox signaling. Dysfunction of mitochondria has been implicated the pathogenesis various brain diseases, including neurodegenerative disorders, stroke, psychiatric illnesses. This review paper provides comprehensive overview intricate relationship between disease, focusing on underlying pathological mechanisms exploring potential therapeutic opportunities. The covers key topics such as mitochondrial DNA mutations, impaired oxidative phosphorylation, dynamics, calcium dysregulation, reactive oxygen species generation context disease. Additionally, it discusses emerging strategies targeting dysfunction, protective agents, metabolic modulators, gene therapy approaches. By critically analysing existing literature recent advancements, this aims to enhance our understanding multifaceted disease shed light novel interventions.
Язык: Английский
Процитировано
65
Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)
Опубликована: Янв. 9, 2025
Abstract Mitochondria are essential for cellular function and viability, serving as central hubs of metabolism signaling. They possess various metabolic quality control mechanisms crucial maintaining normal activities. Mitochondrial genetic disorders can arise from a wide range mutations in either mitochondrial or nuclear DNA, which encode proteins other contents. These defects lead to breakdown metabolism, such the collapse oxidative phosphorylation, one mitochondria’s most critical functions. diseases, common group disorders, characterized by significant phenotypic heterogeneity. Clinical symptoms manifest systems organs throughout body, with differing degrees forms severity. The complexity relationship between mitochondria diseases results an inadequate understanding genotype-phenotype correlation these historically making diagnosis treatment challenging often leading unsatisfactory clinical outcomes. However, recent advancements research technology have significantly improved our management conditions. translations mitochondria-related therapies actively progressing. This review focuses on physiological mitochondria, pathogenesis potential diagnostic therapeutic applications. Additionally, this discusses future perspectives diseases.
Язык: Английский
Процитировано
2
Ageing Research Reviews, Год журнала: 2023, Номер 91, С. 102091 - 102091
Опубликована: Окт. 12, 2023
Язык: Английский
Процитировано
38
Journal of Translational Medicine, Год журнала: 2023, Номер 21(1)
Опубликована: Июль 11, 2023
Abstract Background Alzheimer's disease (AD) is the most common neurodegenerative disease. Mitochondrial dysfunction and immune responses are important factors in pathogenesis of AD, but their crosstalk AD has not been studied. In this study, independent role interaction mitochondria-related genes cell infiltration were investigated using bioinformatics methods. Methods The datasets obtained from NCBI Gene Expression Omnibus (GEO), data mitochondrial was MitoCarta3.0 database. Subsequently, differential expression (DEGs) screening GSEA functional enrichment analysis performed. intersection DEGs related used to obtain MitoDEGs. MitoDEGs relevant determined by Least absolute shrinkage selection operator multiple support vector machine recursive feature elimination, as well protein–protein interactions (PPI) network random forest. 28 kinds cells analyzed ssGSEA, relationship between hub proportion levels verified models mice, OPA1 damage neuronal apoptosis investigated. Results functions pathways significantly enriched including response activation, IL1R pathway, metabolism, oxidative electron transport chain-oxphos system mitochondria. Hub closely based on PPI network, forest two learning algorithms. Five associated with neurological disorders identified biological function examination. found be correlated memory B cell, effector CD8 T activated dendritic natural killer type 17 helper Neutrophil, MDSC, plasmacytoid cell. These can also predict risk have good diagnostic efficacy. addition, mRNA BDH1, TRAP1, OPA1, DLD mice consistent results analysis, SPG7 showed a downward trend. Meanwhile, overexpression alleviated induced Aβ1-42. Conclusions potential identified. Their microenvironment may play crucial occurrence prognosis which provides new insight for studying exploring targets.
Язык: Английский
Процитировано
30
Alzheimer s & Dementia, Год журнала: 2023, Номер 19(11), С. 5159 - 5172
Опубликована: Май 9, 2023
Females with Alzheimer's disease (AD) suffer accelerated dementia and loss of cholinergic neurons compared to males, but the underlying mechanisms are unknown. Seeking causal contributors both these phenomena, we pursued changes in transfer RNS (tRNA) fragments (tRFs) targeting transcripts (CholinotRFs).
Язык: Английский
Процитировано
28