The mitochondrial hypothesis: Dysfunction, bioenergetic defects, and the metabolic link to Alzheimer's disease

Publication date: Available online 10 July 2020Source: International Review of NeurobiologyAuthor(s): Russell H. Swerdlow
Source: International Review of Neurobiology - Category: Neuroscience Source Type: research

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In this study, we examined the effects of oxytocin on the Aβ-induced impairment of synaptic plasticity in mice. To investigate the effect of oxytocin on synaptic plasticity, we prepared acute hippocampal slices for extracellular recording and assessed long-term potentiation (LTP) with perfusion of the Aβ active fragment (Aβ25-35) in the absence and presence of oxytocin. We found that oxytocin reversed the impairment of LTP induced by Aβ25-35 perfusion in the mouse hippocampus. These effects were blocked by pretreatment with the selective oxytocin receptor antagonist L-368,899. Furthermore, the tr...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Publication date: 2020Source: International Review of Neurobiology, Volume 154Author(s): Russell H. Swerdlow
Source: International Review of Neurobiology - Category: Neuroscience Source Type: research
Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disorder with cardinal manifestation of cognitive dysfunction. The limitation to avail a successful drug candidate encourages researchers to establish an appropriate animal model in the novel anti-AD drug discovery process. In this context, the mechanism of mitochondrial dysfunction in cognitive deficit animals is yet to be established for intracerebroventricular injection of streptozotocin (ICV-STZ). Experimental dementia was induced in male rats by ICV-STZ on day-1 (D-1) of the experimental protocol at a sub-diabetogenic dose (3 mg/kg) twi...
Source: Experimental Brain Research - Category: Neuroscience Authors: Tags: Exp Brain Res Source Type: research
Abstract Neurological disorders (ND) are the central nervous system (CNS) related complications originated by enhanced oxidative stress, mitochondrial failure and overexpression of proteins like S100B. S100B is a helix-loop-helix protein with calcium-binding domain associated to various neurological disorders through activation of MAPK pathway, increased NFkB expression results in cell survival, proliferation and gene up-regulation. S100B protein plays a crucial role in Alzheimer's disease, Parkinson's disease, multiple sclerosis, Schizophrenia and epilepsy because high expression of this protein directly targets ...
Source: Current Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Curr Neuropharmacol Source Type: research
Abstract BACKGROUND: The apolipoprotein E (APOE) ε4 allele is a strong risk factor for Alzheimer's disease (AD) in Caucasian and African American populations. It suggests that other genetic factors may modulate AD pathogenesis in Chinese populations, among which the frequency of this allele is reduced but the AD prevalence is maintained. The translocase of outer mitochondrial membrane 40 (TOMM40), which is located adjacent to APOE, may play an APOE-dependent role in modulating AD pathogenesis. AIMS: This work aimed to investigate whether TOMM40 polymorphisms modulate AD risk independently of, or in co...
Source: Aging Clinical and Experimental Research - Category: Geriatrics Authors: Tags: Aging Clin Exp Res Source Type: research
As a general rule, one should be skeptical about any and all single studies that identify longevity-associated genes from human data. Typically the results cannot be replicated in different study populations, and the effect sizes are in any case small. Identified gene variants confer only small changes in the odds of reaching a given age. Only a handful of gene variants show up reliably in multiple studies carried out in different human populations. So, unfortunately, however interesting or novel the data in a new study, such as the association of longevity with maintenance of normal iron levels noted in today's open acces...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
Abstract Oxidative stress is considered as one of the pathogenesis of Alzheimer's disease (AD) and plays an important role in the occurrence and development of AD. Nuclear factor erythroid 2 related factor 2 (NRF2) is a key regulatory of oxidative stress defence. There is growing evidence indicating the relationship between NRF2 and AD. NRF2 activation mitigates multiple pathogenic processes involved in AD by upregulating antioxidative defense, inhibiting neuroinflammation, improving mitochondrial function, maintaining proteostasis, and inhibiting ferroptosis. In addition, several NRF2 activators are currently bei...
Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research
In this study, we applied a well studied prediction model developed on data from five CpG sites, to increase the practicability of these tests. We have determined the biological age of the heart, specifically of the right atrium (RA) and left atrium (LA), and of peripheral blood leucocytes, by measuring the mitotic telomere length (TL) and the non-mitotic epigenetic age (DNAmAge). We found that DNAmAge, of both atrial tissues (RA and LA), was younger in respect to the chronological age (-12 years). Furthermore, no significant difference existed between RA and LA, suggesting that, although anatomically diverse and ex...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Based on amyloid cascade and tau hypotheses, protein biomarkers of different A β and tau species in cerebrospinal fluid (CSF) and blood/plasma/serum have been examined to correlate with brain pathology. Recentl...
Source: Molecular Neurodegeneration - Category: Neurology Authors: Tags: Research article Source Type: research
AbstractThe understanding of how aging contributes to dementia remains obscure. To address this problem, a chemical biology approach was used employing CAD031, an Alzheimer ’s disease (AD) drug candidate identified using a discovery platform based upon phenotypic screens that mimic toxicities associated with the aging brain. Since CAD031 has therapeutic efficacy when fed to old symptomatic transgenic AD mice, the chemical biology hypothesis is that it can be used to determine the molecular pathways associated with age-related disease by identifying those that are modified by the compound. Here we show that when CAD03...
Source: AGE - Category: Geriatrics Source Type: research
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