Biochemical Pharmacology, Год журнала: 2023, Номер 215, С. 115717 - 115717
Опубликована: Июль 28, 2023
Язык: Английский
Ageing Research Reviews, Год журнала: 2022, Номер 77, С. 101619 - 101619
Опубликована: Апрель 5, 2022
Язык: Английский
Процитировано
411
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
114
Frontiers in Aging Neuroscience, Год журнала: 2022, Номер 14
Опубликована: Март 22, 2022
Iron plays a crucial role in many physiological processes of the human body, but iron is continuously deposited brain as we age. Early studies found overload directly proportional to cognitive decline Alzheimer’s disease (AD). Amyloid precursor protein (APP) and tau protein, both which are related AD pathogenesis, associated with metabolism. A variety metabolism-related proteins have been be abnormally expressed brains patients mouse models, resulting deposition promoting progression. β (Aβ) hyperphosphorylated tau, two pathological hallmarks AD, can also promote brain, forming vicious cycle development-iron deposition. subsequent ferroptosis has potential mechanism underlying neuronal loss neurodegenerative diseases. chelators, antioxidants hepcidin were useful for treating represents an important direction treatment research drug development future. The review explored deep connection between dysregulation discussed new hypothesis dyshomeostasis ferroptosis, summarized therapeutics capable targeting iron, expectation draw more attention corresponding development.
Язык: Английский
Процитировано
104
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
Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)
Опубликована: Март 1, 2024
Abstract Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family (PGC-1s), consisting of three members encompassing PGC-1α, PGC-1β, and PGC-1-related coactivator (PRC), was discovered more than a quarter-century ago. PGC-1s are essential coordinators many vital cellular events, including mitochondrial functions, oxidative stress, endoplasmic reticulum homeostasis, inflammation. Accumulating evidence has shown that implicated in diseases, such as cancers, cardiac diseases cardiovascular neurological disorders, kidney motor system metabolic disorders. Examining the upstream modulators co-activated partners identifying critical biological events modulated by downstream effectors contribute to presentation elaborate network PGC-1s. Furthermore, discussing correlation between well summarizing therapy targeting helps make individualized precise intervention methods. In this review, we summarize basic knowledge regarding molecular regulatory network, discuss physio-pathological roles human review application PGC-1s, diagnostic prognostic value several therapies pre-clinical studies, suggest directions for future investigations. This presents immense potential treatment hopefully facilitates promotion new therapeutic targets.
Язык: Английский
Процитировано
75
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
Translational Neurodegeneration, Год журнала: 2023, Номер 12(1)
Опубликована: Фев. 27, 2023
Abstract Physical exercise is of great significance for maintaining human health. Exercise can provide varying degrees benefits to cognitive function at all stages life cycle. Currently, with the aging world’s population and increase expectancy, dysfunction has gradually become a disease high incidence, which accompanied by neurodegenerative diseases in elderly individuals. Patients often exhibit memory loss, aphasia weakening orientation once diagnosed, are unable have normal life. Cognitive largely affects physical mental health, reduces quality life, causes economic burden society. At present, most interventions aimed maintain current level delay deterioration cognition. In contrast, as nonpharmacological therapy advantages its nontoxicity, low cost universal application. The molecular mechanisms underlying effect on cognition complex, studies been extensively centered neural plasticity, direct target brain. addition, mitochondrial stability energy metabolism essential brain status. Meanwhile, organ-brain axis responds induces release cytokines related this review, we summarize latest evidence effects cognition, point out directions future research.
Язык: Английский
Процитировано
51
Frontiers in Pharmacology, Год журнала: 2023, Номер 14
Опубликована: Янв. 26, 2023
Alzheimer’s disease (AD) is the most common type of dementia in elderly. Several hypotheses emerged from AD pathophysiological mechanisms. However, no neuronal protective or regenerative drug available nowadays. Researchers still work development and are finding new molecular targets to treat AD. Therefore, this study aimed summarize main advances pharmacological therapy. Clinical trials registered National Library Medicine database were selected analyzed accordingly targets, therapeutic effects, safety profile. The outcome was lack efficacy. Only seven concluded that tested drugs safe induced any kind improvement. Three works showed effects followed by toxicity. In addition aducanumab recent FDA approval, antibodies against amyloid-β (Aβ) noteworthy results. 5-HT6 antagonists, tau inhibitors nicotinic agonists’ data discouraging. anti-Aβ vaccine, BACE inhibitor anti-neuroinflammation promising
Язык: Английский
Процитировано
50
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(2), С. 1168 - 1168
Опубликована: Янв. 18, 2024
Alzheimer’s Disease (AD) is the most common neurodegenerative disease which manifests with progressive cognitive impairment, leading to dementia. Considering noninvasive collection of saliva, we designed systematic review answer question “Are salivary biomarkers reliable for diagnosis Disease?” Following inclusion and exclusion criteria, 30 studies were included in this (according PRISMA statement guidelines). Potential include mainly proteins, metabolites even miRNAs. Based on meta-analysis, AD patients, levels beta-amyloid42 p-tau significantly increased, t-tau lactoferrin decreased at borderline statistical significance. However, according pooled AUC, showed a significant predictive value salivary-based diagnosis. In conclusion, potential markers such as beta-amyloid42, tau can be detected saliva could reliably support early disease.
Язык: Английский
Процитировано
17
Ageing Research Reviews, Год журнала: 2024, Номер 98, С. 102335 - 102335
Опубликована: Май 12, 2024
Язык: Английский
Процитировано
16