Cellular Maintenance Mechanisms Struggle to Break Down TDP-43 Aggregates, Leading to Neurodegeneration

The most common age-related neurodegenerative conditions are associated with the build up of various protein aggregates, chemically altered or misfolded proteins that can form solid deposits in and around cells when in that state. These protein aggregates are characterized by the ability to spread and grow, acting as seeds for more aggregation. They include the well known amyloid-β and tau of Alzheimer's disease, the α-synuclein associated with Parkinson's disease, and so forth. In recent years researchers have been devoting ever more effort to investigations of a less well known protein aggregate, TDP-43, associated with ALS and frontotemporal lobar degeneration. Today's open access paper is representative of work taking place to understand TDP-43 aggregates and how and why they form in the aging brain. The goal of research into protein aggregates is to either find a way to remove them, or to find a way to prevent them from forming in the first place. Protein aggregation is a feature of old people, not young people, despite the fact that the mechanisms that can give rise to aggregation are present throughout life. Thus the damage and change of aging, the rising dysfunction in near all cellular processes, is in some way involved in allowing the presence of protein aggregates to rise to pathological levels. In the research here, the finger is pointed at age-related impairment of the cellular housekeeping systems of the proteasome and autophagy, both of which ...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs

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Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
In this study, metallurgical-slag-based binder (MSB) with different dosages of calcium hydroxide (CH) was mixed with high-arsenic-containing mine tailings (HAMT) to form green mining fill samples (GMFs) for As solidification/stabilisation (S/S). The As leaching characteristics of the GMFs were evaluated using pH-dependent leaching tests, semi-dynamic leaching tests and toxicity leaching tests. The effective diffusion coefficient (De) decreased from 6.98 × 10−14 to 5.90 × 10−15 cm2/s and the leachability index (LI) increased from 13.53 to 14.73 after 3 wt.% C...
Source: Journal of Hazardous Materials - Category: Environmental Health Source Type: research
Dementia is a global health problem, with the World Health Organization estimates placing the number of afflicted persons at around 50 million worldwide.1 Without a treatment or cure, projections are that numbers will increase dramatically around the world by 2050.2 The prevalent intervention strategy has been pursuit of a drug to cure this illness or to modify the illness course. Available medications, mainly approved for use in Alzheimer's-type dementia (AD) but extended empirically to other forms, are mainly palliative with only modest benefits in a subset of patients.
Source: Journal of the American Medical Directors Association - Category: Health Management Authors: Tags: Editorial Source Type: research
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Source: Annals of Physical and Rehabilitation Medicine - Category: Rehabilitation Source Type: research
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Source: Journal of the American College of Nutrition - Category: Nutrition Authors: Source Type: research
In this study, methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced nigrostriatal neurodegeneration and astro-glial activations were determined by western blot and immunofluorescence techniques in wild type (WT) mice, MC-deficient (MC-KO) mice and GMF-deficient (GMF-KO) mice, with or without MC reconstitution before MPTP administration. We show that GMF-KO in the MCs reduces the synergistic effects of MC and Calpain1 (calcium-activated cysteine protease enzyme)-dependent dopaminergic neuronal loss that reduces motor behavioral impairments in MPTP-treated mouse. Administration of MPTP increase in calpain-mediated prote...
Source: Brain, Behavior, and Immunity - Category: Neurology Source Type: research
AbstractHebbian plasticity means that if the firing of two neurons is correlated, then their connection is strengthened. Conversely, uncorrelated firing causes a decrease in synaptic strength. Spike-timing-dependent plasticity (STDP) represents one instantiation of Hebbian plasticity. Under STDP, synaptic changes depend on the relative timing of the pre- and post-synaptic firing. By inducing pre- and post-synaptic firing at different relative times the STDP curves of many neurons have been determined, and it has been found that there are different curves for different neuron types or synaptic sites. Biophysically, strength...
Source: Journal of Computational Neuroscience - Category: Neuroscience Source Type: research
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Source: Current Pharmaceutical Design - Category: Drugs & Pharmacology Authors: Tags: Curr Pharm Des Source Type: research
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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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Source: Food and Chemical Toxicology - Category: Food Science Authors: Tags: Food Chem Toxicol Source Type: research
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