Cellular and Molecular Neurobiology, Journal Year: 2023, Volume and Issue: 43(7), P. 3115 - 3136
Published: May 25, 2023
Language: Английский
International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(21), P. 12841 - 12841
Published: Oct. 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
Language: Английский
Citations
187
International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(21), P. 12924 - 12924
Published: Oct. 26, 2022
Alzheimer’s disease (AD), is a progressive neurodegenerative that affects behavior, thinking, learning, and memory in elderly individuals. AD occurs two forms, early onset familial late-onset sporadic; genetic mutations PS1, PS2, APP genes cause AD, combination of lifestyle, environment factors causes the sporadic form disease. However, accelerated progression noticed patients with AD. Disease-causing pathological changes are synaptic damage, mitochondrial structural functional changes, addition to increased production accumulation phosphorylated tau (p-tau), amyloid beta (Aβ) affected brain regions patients. Aβ peptide derived from precursor protein (APP) by proteolytic cleavage gamma secretases. glycoprotein plays significant role maintaining neuronal homeostasis like signaling, development, intracellular transport. reported have both protective toxic effects neurons. The purpose our article summarize recent developments its association synapses, mitochondria, microglia, astrocytes, interaction p-tau. Our also covers therapeutic strategies reduce toxicities discusses reasons for failures therapeutics.
Language: Английский
Citations
177
Biochimie, Journal Year: 2021, Volume and Issue: 195, P. 100 - 113
Published: Nov. 24, 2021
Language: Английский
Citations
153
Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)
Published: Aug. 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.
Language: Английский
Citations
135
Free Radical Biology and Medicine, Journal Year: 2022, Volume and Issue: 193, P. 134 - 157
Published: Oct. 4, 2022
Language: Английский
Citations
128
Free Radical Biology and Medicine, Journal Year: 2021, Volume and Issue: 172, P. 652 - 667
Published: July 8, 2021
Language: Английский
Citations
127
Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 148, P. 112681 - 112681
Published: Feb. 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.
Language: Английский
Citations
126
Frontiers in Neuroscience, Journal Year: 2022, Volume and Issue: 16
Published: Sept. 1, 2022
Currently, there is no disease-modifying treatment available for Alzheimer's and Parkinson's disease (AD PD) that includes the highly controversial approval of Aβ-targeting antibody aducanumab AD. Hence, still an unmet need a neuroprotective drug in both AD PD. Type 2 diabetes risk factor Glucagon-like peptide 1 (GLP-1) hormone growth has shown effects preclinical studies, success GLP-1 mimetics phase II clinical trials PD raised new hope. are currently on market as treatments type diabetes. analogs safe, well tolerated, resistant to desensitization characterized clinic. Herein, we review existing evidence illustrate pathways induced following GLP-1R activation neurons, microglia astrocytes. The latter include synaptic protection, improvements cognition, learning motor function, amyloid pathology-ameliorating properties (Aβ, Tau, α-synuclein), suppression Ca
Language: Английский
Citations
111
Ageing Research Reviews, Journal Year: 2021, Volume and Issue: 73, P. 101529 - 101529
Published: Nov. 20, 2021
Language: Английский
Citations
104
Journal of Neuroinflammation, Journal Year: 2022, Volume and Issue: 19(1)
Published: Oct. 6, 2022
Abstract Alzheimer's disease (AD) is the most common neurodegenerative in elderly globally. Emerging evidence has demonstrated microglia-driven neuroinflammation as a key contributor to onset and progression of AD, however, mechanisms that mediate remain largely unknown. Recent studies have suggested mitochondrial dysfunction including DNA (mtDNA) damage, metabolic defects, quality control (QC) disorders precedes microglial activation subsequent neuroinflammation. Therefore, an in-depth understanding relationship between AD important unveil pathogenesis develop effective approaches for early diagnosis treatment. In this review, we summarized current progress roles mtDNA, metabolism, QC changes provide comprehensive thoughts targeting mitochondria potential therapeutic strategies AD.
Language: Английский
Citations
82