Brain , recently renamed as wasteosomes, are polyglucosan bodies that appear during aging and some neurodegenerative conditions. They collect waste substances and are part of a brain cleaning mechanism. For decades, studies on their composition have produced inconsistent results and the presence of tau protein in them has been controversial. In this work, we reanalyzed the presence of this protein in wasteosomes and we pointed out a methodological problem when immunolabeling. It is well known that to detect tau it is necessary to perform an antigen retrieval. However, in the case of wasteosomes, an excessive antigen retrieval with boiling dissolves their polyglucosan structure, releases the entrapped proteins and, thus, prevents their detection. After performing an adequate pre-treatment, with an intermediate time of boiling, we observed that some brain wasteosomes from patients with Alzheimer's disease (AD) contained tau, while we did not detect tau protein in those from non-AD patients. These observations pointed the different composition of wasteosomes depending on the neuropathological condition and reinforce the role of wasteosomes as waste containers.
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http://dx.doi.org/10.3389/fnagi.2023.1110425 | DOI Listing |
J Int Neuropsychol Soc
January 2025
Department of Brain Health, University of Nevada, Las Vegas, NV, USA.
Objective: Neuropsychiatric symptoms (NPS) are considered diagnostic and prognostic indicators of dementia and are attributable to neurodegenerative processes. Little is known about the prognostic value of early NPS on executive functioning (EF) decline in Alzheimer's disease and related dementias (ADRD). We examined whether baseline NPS predicted the rate of executive function (EF) decline among older adults with ADRD.
View Article and Find Full Text PDFIntroduction: Age-associated depletion in nicotinamide adenine dinucleotide (NAD+) concentrations has been implicated in metabolic, cardiovascular, and neurodegenerative disorders. Supplementation with NAD+ precursors, such as nicotinamide riboside (NR), offers a potential therapeutic avenue against neurodegenerative pathologies in aging, Alzheimer's disease, and related dementias. A crossover, double-blind, randomized placebo (PBO) controlled trial was conducted to test the safety and efficacy of 8 weeks' active treatment with NR (1 g/day) on cognition and plasma AD biomarkers in older adults with subjective cognitive decline and mild cognitive impairment.
View Article and Find Full Text PDFACS Pharmacol Transl Sci
January 2025
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Sigma 1 receptor (S1R) is a multifunctional, ligand-activated protein located in the membranes of the endoplasmic reticulum (ER). It mediates a variety of neurological disorders, including epilepsy, amyotrophic lateral sclerosis, Alzheimer's disease, Huntington's disease. The wide neuroprotective effects of S1R agonists are achieved by a variety of pro-survival and antiapoptotic S1R-mediated signaling functions.
View Article and Find Full Text PDFTheranostics
January 2025
Xiamen Key Laboratory of Brain Center, The First Affiliated Hospital of Xiamen University, and Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, Xiamen University, Xiamen, China.
Mutations in the synaptic protein MAM domain containing glycosylphosphatidylinositol anchor 2 (MDGA2) have been associated with autism spectrum disorder (ASD). Therefore, elucidating the regulatory mechanisms of MDGA2 can help develop effective treatments for ASD. Liquid chromatography-tandem mass spectrometry was carried out to identify proteins interacting with the extracellular domain of RPS23RG1 and with MDGA2, followed by co-immunoprecipitation assays to confirm protein-protein interactions.
View Article and Find Full Text PDFBrain Commun
January 2025
Science for Life Laboratory, KTH-Royal Institute of Technology, Stockholm 17165, Sweden.
Parkinson's disease is primarily marked by mitochondrial dysfunction and metabolic abnormalities. We recently reported that the combined metabolic activators improved the immunohistochemical parameters and behavioural functions in Parkinson's disease and Alzheimer's disease animal models and the cognitive functions in Alzheimer's disease patients. These metabolic activators serve as the precursors of nicotinamide adenine dinucleotide and glutathione, and they can be used to activate mitochondrial metabolism and eventually treat mitochondrial dysfunction.
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