Deregulation of excitatory neurotransmission underlying synapse failure in Alzheimer's disease DOI Open Access
Andrea Paula-Lima,

Jordano Brito‐Moreira,

Sérgio T. Ferreira

и другие.

Journal of Neurochemistry, Год журнала: 2013, Номер 126(2), С. 191 - 202

Опубликована: Май 13, 2013

Abstract Alzheimer′s disease ( AD ) is the most common form of dementia in elderly. Memory loss increasingly attributed to soluble oligomers amyloid‐β peptide (AβOs), toxins that accumulate brains and target particular synapses. Glutamate receptors appear be centrally involved synaptic targeting by AβOs. Once bound neurons, AβOs dysregulate activity reduce surface expression both N ‐methyl‐ d ‐aspartate NMDA 2‐amino‐3‐(3‐hydroxy‐5‐methyl‐isoxazol‐4‐yl)propanoic acid AMPA types glutamate receptors, impairing signaling pathways plasticity. In extracellular milieu, promote accumulation excitatory amino acids, ‐serine. This leads overactivation triggering abnormal calcium signals with noxious impacts on neurons. Here, we review key findings linking deregulated neurotransmission implicating this as a primary mechanism synapse failure . We also discuss strategies counteract impact neurotransmission. particular, evidence showing inducing neuronal hyperpolarization via activation inhibitory GABA A prevents AβO‐induced excitotoxicity, suggesting could comprise possible therapeutic approach

Язык: Английский

Regulation of autophagy by mTOR-dependent and mTOR-independent pathways: autophagy dysfunction in neurodegenerative diseases and therapeutic application of autophagy enhancers DOI
Sovan Sarkar

Biochemical Society Transactions, Год журнала: 2013, Номер 41(5), С. 1103 - 1130

Опубликована: Сен. 23, 2013

Autophagy is an intracellular degradation pathway essential for cellular and energy homoeostasis. It functions in the clearance of misfolded proteins damaged organelles, as well recycling cytosolic components during starvation to compensate nutrient deprivation. This process regulated by mTOR (mammalian target rapamycin)-dependent mTOR-independent pathways that are amenable chemical perturbations. Several small molecules modulating autophagy have been identified potential therapeutic application diverse human diseases, including neurodegeneration. Neurodegeneration-associated aggregation-prone predominantly degraded therefore stimulating this with inducers beneficial a wide range transgenic disease models. Emerging evidence indicates compromised contributes aetiology various neurodegenerative diseases related protein conformational disorders causing accumulation mutant toxicity. Combining knowledge dysfunction mechanism drug action may thus be rational designing targeted therapy. The present review describes signalling regulating mammalian highlights disorders.

Язык: Английский

Процитировано

347
The Physiological Roles of Amyloid-β Peptide Hint at New Ways to Treat Alzheimer's Disease DOI Creative Commons
Holly M. Brothers, Maya L. Gosztyla, Stephen R. Robinson

и другие.

Frontiers in Aging Neuroscience, Год журнала: 2018, Номер 10

Опубликована: Апрель 25, 2018

Amyloid-ß (Aß) is best known as the misfolded peptide that involved in pathogenesis of Alzheimer's disease (AD), and it currently primary therapeutic target attempts to arrest course this disease. This notoriety has overshadowed evidence Aß serves several important physiological functions. present throughout lifespan, been found all vertebrates examined thus far, its molecular sequence shows a high degree conservation. These features are typical factor contributes significantly biological fitness, suggestion supported by functions beneficial for brain. The putative roles include protecting body from infections, repairing leaks blood-brain barrier, promoting recovery injury, regulating synaptic function. Evidence these comes vitro vivo studies, which have shown cellular production rapidly increases response challenge often diminishes upon recovery. further adverse outcomes clinical trials attempted deplete order treat AD. We suggest anti-Aß therapies will produce fewer effects if triggers deposition (e.g. pathogens, hypertension diabetes) addressed first.

Язык: Английский

Процитировано

264
Aβ42 assembles into specific β-barrel pore-forming oligomers in membrane-mimicking environments DOI Open Access

Montserrat Serra-Batiste,

Martí Ninot‐Pedrosa,

Mariam Bayoumi

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2016, Номер 113(39), С. 10866 - 10871

Опубликована: Сен. 12, 2016

Significance Numerous reports indicate that amyloid-β peptide (Aβ) oligomers, considered the pathogenic molecular form of Aβ in Alzheimer´s disease (AD), exert their neurotoxicity within membrane. Therefore, it is critical to characterize them such an environment. Here, we worked with two major variants and handled as if they were membrane proteins. By doing so, found variant most strongly linked AD assembled into stable oligomers adopted a specific structure incorporated membranes pores, feature neurotoxicity. Having access pore-forming offers unique opportunities fully establish involvement AD.

Язык: Английский

Процитировано

256
Diagnosis of Alzheimer’s disease utilizing amyloid and tau as fluid biomarkers DOI Creative Commons
Jinny Claire Lee, Soo‐Jeong Kim, Seungpyo Hong

и другие.

Experimental & Molecular Medicine, Год журнала: 2019, Номер 51(5), С. 1 - 10

Опубликована: Май 1, 2019

Current technological advancements in clinical and research settings have permitted a more intensive comprehensive understanding of Alzheimer's disease (AD). This development knowledge regarding AD pathogenesis has been implemented to produce disease-modifying drugs. The potential for accessible effective therapeutic methods generated need detecting this neurodegenerative disorder during early stages progression because such remedial effects are profound when the initial, prolonged prodromal pathogenesis. aggregation amyloid-β (Aβ) tau isoforms characteristic AD; thus, they considered core candidate biomarkers. However, attempting establish reliability Aβ as biomarkers culminated an amalgamation contradictory results theories biomarker concentrations necessary accurate diagnosis. In review, we consider capabilities limitations fluid collected from cerebrospinal fluid, blood, oral, ocular, olfactory secretions diagnostic tools AD, along with impact integration these settings. Furthermore, evolution criteria novel findings discussed. review is summary reflection ongoing concerted efforts tool implement them procedures. Markers body fluids could help clinicians diagnose before cognitive decline appears. After numerous setbacks treating advanced Alzheimer's, researchers eager identify biological indicators that facilitate earlier detection interception. A by YoungSoo Kim colleagues at Yonsei University South Korea, explores promise 'fluid biomarkers,' which enables diagnosis using (CSF), samples. Shifts CSF levels amyloid beta tau, two proteins central pathology, can reliably monitor at-risk individuals. Although collection unpleasant patients, it remains promising than where current data relatively inconclusive. investigations discover safer, cheaper, reliable shift treatment alleviation prevention introduced.

Язык: Английский

Процитировано

230
TREM2 drives microglia response to amyloid-β via SYK-dependent and -independent pathways DOI Creative Commons
Shoutang Wang, Raki Sudan, Vincent Peng

и другие.

Cell, Год журнала: 2022, Номер 185(22), С. 4153 - 4169.e19

Опубликована: Окт. 1, 2022

Язык: Английский

Процитировано

230
Pathogenesis of synaptic degeneration in Alzheimer's disease and Lewy body disease DOI

Cassia Overk,

Eliezer Masliah

Biochemical Pharmacology, Год журнала: 2014, Номер 88(4), С. 508 - 516

Опубликована: Янв. 22, 2014

Язык: Английский

Процитировано

209
Mechanisms of Alzheimer’s Disease Pathogenesis and Prevention: The Brain, Neural Pathology, N-methyl-D-aspartate Receptors, Tau Protein and Other Risk Factors DOI Open Access
Sayad Kocahan, Zümrüt Doğan

Clinical Psychopharmacology and Neuroscience, Год журнала: 2017, Номер 15(1), С. 1 - 8

Опубликована: Янв. 25, 2017

Other SectionsAbstractINTRODUCTIONBRAIN AND ANATOMYNEURAL MECHANISMSPATHOGENESIS OF ALZHEIMER’S DISEASEALZHEIMER’S DISEASE NMDA RECEPTORSTAU PROTEINBRAIN-DERIVED NEUROTROPHIC FACTOR DISEASEANIMAL MODELS BEHAVIORRISK FACTORSCOGNITIVE RESERVE PREVENTIONCONCLUSIONSFiguresReferences

Язык: Английский

Процитировано

200
Role of Copper in the Onset of Alzheimer’s Disease Compared to Other Metals DOI Creative Commons
Soghra Bagheri, Rosanna Squitti, Thomas Haertlé

и другие.

Frontiers in Aging Neuroscience, Год журнала: 2018, Номер 9

Опубликована: Янв. 23, 2018

Alzheimer's disease (AD) is a neurodegenerative disorder that characterized by amyloid plaques in patients' brain tissue. The are mainly made of β-amyloid peptides and trace elements including Zn

Язык: Английский

Процитировано

192
Eco-friendly synthesis and biomedical applications of gold nanoparticles: A review DOI

Kalimuthu Kalishwaralal,

Byung Seok, Seokjoon Kim

и другие.

Microchemical Journal, Год журнала: 2019, Номер 152, С. 104296 - 104296

Опубликована: Окт. 18, 2019

Язык: Английский

Процитировано

165
Neuroinflammation in Alzheimer’s disease: insights from peripheral immune cells DOI Creative Commons

Qiang Zhang,

Guanhu Yang,

Yuan Luo

и другие.

Immunity & Ageing, Год журнала: 2024, Номер 21(1)

Опубликована: Июнь 14, 2024

Abstract Alzheimer’s disease (AD) is a serious brain disorder characterized by the presence of beta-amyloid plaques, tau pathology, inflammation, neurodegeneration, and cerebrovascular dysfunction. The chronic neuroinflammation, breaches in blood-brain barrier (BBB), increased levels inflammatory mediators are central to pathogenesis AD. These factors promote penetration immune cells into brain, potentially exacerbating clinical symptoms neuronal death AD patients. While microglia, resident nervous system (CNS), play crucial role AD, recent evidence suggests infiltration cerebral vessels parenchyma peripheral cells, including neutrophils, T lymphocytes, B NK monocytes participate regulation immunity which expected huge future immunotherapy. Given this article seeks offer comprehensive overview their contributions neuroinflammation disease. Understanding these neuroinflammatory response vital for developing new diagnostic markers therapeutic targets enhance diagnosis treatment

Язык: Английский

Процитировано

22