ASAP Proteomic Profiles of the Early Mitochondrial Changes in APP/PS1 and ApoE4 Transgenic Mice Models of Alzheimer ’s Disease

Journal of Proteome ResearchDOI: 10.1021/acs.jproteome.9b00136
Source: Journal of Proteome Research - Category: Biochemistry Authors: Source Type: research

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A fair amount of effort is presently put towards the exploration of supplements derived from vitamin B3 compounds (nicotinamide, niacin, nicotinamide riboside) that act as precursors to enable the manufacture of nicotinamide adenine dinucleotide (NAD). NAD is an important component in mitochondrial activity, and levels decline with age. Some portion of the loss of mitochondrial function, implicated in the progression of many age-related conditions, is due to NAD insufficiency. There is a rich history of the use of high doses of vitamin B3 as an intervention, most of it predating modern understanding of the role of NAD in m...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
Abstract The two most common aging-related diseases, Alzheimer's disease and type 2 diabetes mellitus, are associated with accumulation of amyloid proteins (β-amyloid and amylin, respectively). This amylin aggregation is reportedly cytotoxic to neurons. We found that aggregation of human amylin (hAmylin) induced neuronal apoptosis without obvious microglial infiltration in vivo. High concentrations of hAmylin irreversibly aggregated on the surface of the neuronal plasma membrane. Long-term incubation with hAmylin induced morphological changes in neurons. Moreover, hAmylin permeabilized the neuronal membrane w...
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research
Abstract Maternally inherited RNA and proteins control much of embryonic development. The effect of such maternal information beyond embryonic development is largely unclear. Here, we report that maternal contribution of histone H3.3 assembly complexes can prevent the expression of late-onset anatomical, physiologic, and behavioral abnormalities of C. elegans. We show that mutants lacking hira-1, an evolutionarily conserved H3.3-deposition factor, have severe pleiotropic defects that manifest predominantly at adulthood. These late-onset defects can be maternally rescued, and maternally derived HIRA-1 protein ...
Source: Current Biology - Category: Biology Authors: Tags: Curr Biol Source Type: research
The role of mitochondrial impairment on Alzheimer´s disease neurodegeneration: the Tau connection. Curr Neuropharmacol. 2020 May 24;: Authors: Quntanilla RA, Tapia-Monsalves C Abstract Accumulative evidence has shown that mitochondrial dysfunction plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). Mitochondrial impairment actively contributes to the synaptic and cognitive failure that characterizes AD. The presence of soluble pathological forms of tau like hyperphosphorylated at Ser396 and Ser404 and cleaved at Asp421 by caspase 3, negatively impacts mitochondrial bioenergetic...
Source: Current Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Curr Neuropharmacol Source Type: research
AbstractAlthough the pathogenesis of neurodegenerative diseases is still widely unclear, various mechanisms have been proposed and several pieces of evidence are supportive for an important role of mitochondrial dysfunction. The present review provides a comprehensive and up-to-date overview about the role of mitochondria in the two most common neurodegenerative disorders: Alzheimer ’s disease (AD) and Parkinson’s disease (PD). Mitochondrial involvement in AD is supported by clinical features like reduced glucose and oxygen brain metabolism and by numerous microscopic and molecular findings, including altered m...
Source: Molecular Neurobiology - Category: Neurology Source Type: research
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive impairment that increasingly afflicts the elderly population. Soluble oligomers (AβOs) has been implicated in AD pathogenesis: however, the molecular events underlying a role for Aβ are not well understood. We studied the effects of AβOs on mitochondrial function and on key proteins that regulate mitochondrial dynamics and biogenesis in hippocampal neurons and PC-12 cells. We find that AβOs treatment caused a reduction in total Mfn1 after a 2 h exposure (42 ± 11%); while DRP1 increased at 1 and 2 h (205 ± 2...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Methylation of mitochondrial tRNAs (mt-tRNA) at the 9th position ( “p9 site”) is known to impact translational efficiency and downstream mitochondrial function; however, direct assessment of mt-RNA methylation ...
Source: BMC Medical Genomics - Category: Genetics & Stem Cells Authors: Tags: Research article Source Type: research
AbstractAlzheimer ’s disease (AD) is a progressive neurodegenerative disease involving aggregation of misfolded proteins inside the neuron causing prolonged cellular stress. The neuropathological hallmarks of AD include the formation of senile plaques and neurofibrillary tangles in specific brain regions that lead to synaptic loss and neuronal death. The exact mechanism of neuron dysfunction in AD remains obscure. In recent years, endoplasmic reticulum (ER) dysfunction has been implicated in neuronal degeneration seen in AD. Apart from AD, many other diseases also involve misfolded proteins aggregations in th e ER, a...
Source: Molecular Neurobiology - Category: Neurology Source Type: research
This study provides direct evidence for the contribution of gut microbiota to the cognitive decline during normal aging and suggests that restoring microbiota homeostasis in the elderly may improve cognitive function. On Nutraceutical Senolytics https://www.fightaging.org/archives/2020/05/on-nutraceutical-senolytics/ Nutraceuticals are compounds derived from foods, usually plants. In principle one can find useful therapies in the natural world, taking the approach of identifying interesting molecules and refining them to a greater potency than naturally occurs in order to produce a usefully large therape...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, we found that older nematodes have higher ROS levels. Interestingly, after hydrogen treatment, the ROS levels were significantly decreased, and hydrogen could significantly extend the lifespans of the N2, sod-3 and sod-5 mutant strains, by approximately 22.7%, 9.5%, and 8.7%, respectively. In addition, aging is regulated by a variety of pathways, such as the insulin signaling pathway, the rapamycin target signaling pathway, and the caloric restriction pathway. However, our results showed that the lifespans of the daf-2 and daf-16 strains, in which these pathways are upregulated, were not affected afte...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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