Brain clusterin protein isoforms and mitochondrial localization

In this study, we use multiple rodent and human brain tissue and neural cell models to demonstrate that CLU is expressed as multiple isoforms that have distinct cellular or subcellular localizations in the brain. Of particular significance, we identify a non-glycosylated 45 kDa CLU isoform (mitoCLU) that is localized to the mitochondrial matrix and expressed in both rodent and human neurons and astrocytes. In addition, we show that rodent mitoCLU is translated from a non-canonical CUG (Leu) start site in Exon 3, a site that coincides with an AUG (Met) in human CLU. Last, w e reveal that mitoCLU is present at the gene and protein level in the currently available CLU–/– mouse model. Collectively, these data provide foundational knowledge that is integral in elucidating the relationship between CLU and the development of LOAD.
Source: eLife - Category: Biomedical Science Tags: Neuroscience Source Type: research

Related Links:

Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
β-amyloid and oxidative stress: perspectives in drug development. Curr Pharm Des. 2019 Dec 08;: Authors: Caruso G, Spampinato SF, Cardaci V, Caraci F, Sortino MA, Merlo S Abstract Alzheimer's Disease (AD) is a slow-developing neurodegenerative disorder in which a main pathogenic role has been assigned to β-amyloid protein (Aβ) that accumulates in extracellular plaques. The mechanism of action of Aβ has been deeply analyzed and several membrane structure have been identified as potential mediators of its effect. The ability of Aβ to modify neuronal activity, receptor expression...
Source: Current Pharmaceutical Design - Category: Drugs & Pharmacology Authors: Tags: Curr Pharm Des Source Type: research
Publication date: 1 January 2020Source: Neuroscience, Volume 424Author(s): Eva-Lotta von Rüden, Christina Zellinger, Julia Gedon, Andreas Walker, Vera Bierling, Cornelia A. Deeg, Stefanie M. Hauck, Heidrun PotschkaAbstractClinical evidence and pathological studies suggest a bidirectional link between temporal lobe epilepsy and Alzheimer’s disease (AD). Data analysis from omic studies offers an excellent opportunity to identify the overlap in molecular alterations between the two pathologies.We have subjected proteomic data sets from a rat model of epileptogenesis to a bioinformatics analysis focused on proteins ...
Source: Neuroscience - Category: Neuroscience Source Type: research
Authors: Seo DY, Heo JW, Ko JR, Kwak HB Abstract Neuroinflammation is a central pathological feature of several acute and chronic brain diseases, including Alzheimer disease (AD), Parkinson disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). It induces microglia activation, mitochondrial dysfunction, the production of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), pro-inflammatory cytokines, and reactive oxygen species. Exercise, which plays an important role in maintaining and improving brain health, might be a highly effective intervention for preventing ...
Source: International Neurourology Journal - Category: Urology & Nephrology Tags: Int Neurourol J Source Type: research
Apolipoprotein E regulates mitochondrial function through the PGC-1α-sirtuin 3 pathway. Aging (Albany NY). 2019 Dec 06;11: Authors: Yin J, Nielsen M, Carcione T, Li S, Shi J Abstract Cerebral hypometabolism is a pathophysiological hallmark of Alzheimer's disease (AD). Our previous studies found that a mitochondrial protein, sirtuin3 (Sirt3), was down-regulated in human AD postmortem brains. Sirt3 protected neurons against oligo-amyloid β-42 induced hypometabolism in human Apolipoprotein E4 (ApoE4) transgenic mice. However, how ApoE affects mitochondrial function and its proteins such as Sir...
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research
Abstract Neurodegenerative disease refers to a range of chronic and progressive disorders that are characterized by dysfunction and loss of neurons. Neurodegeneration involves protein misfolding, oxidative injury, impaired mitochondrial function, neurotrophin deficiency and may also involve neuroinflammation. The sirtuin family of proteins plays a key role in this process suggesting that modulation of sirtuin can modify disease progression. This review examines experimental and clinical evidence relating to the potential role of SIRT1 and SIRT2, and their modulators in neurodegenerative diseases. Both neuroprotect...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research
AbstractAging of the microcirculatory network plays a central role in the pathogenesis of a wide range of age-related diseases, from heart failure to Alzheimer ’s disease. In the eye, changes in the choroid and choroidal microcirculation (choriocapillaris) also occur with age, and these changes can play a critical role in the pathogenesis of age-related macular degeneration (AMD). In order to develop novel treatments for amelioration of choriocapillaris aging and prevention of AMD, it is essential to understand the cellular and functional changes that occur in the choroid and choriocapillaris during aging. In this re...
Source: AGE - Category: Geriatrics Source Type: research
Publication date: Available online 2 December 2019Source: Neurochemistry InternationalAuthor(s): Hiroshi Higashi, Toshihiko Kinjo, Kyosuke Uno, Nobuyuki KuramotoAbstractExcitotoxicity has been believed to be one of the causes of neurodegenerative diseases such as Alzheimer's disease and Huntington's disease. So far, much research has been done to suppress the neuronal excessive excitations, however, we still have not achieved full control, which may be due to the lack of some factors. As a matter of course, there is an urgent need to clarify all mechanisms that inhibit the onset and progression of neurodegenerative disease...
Source: Neurochemistry International - Category: Neuroscience Source Type: research
In conclusion, T2D impairs vascular function by dysregulated autophagy. Therefore, autophagy could be a potential target for overcoming diabetic microvascular complications. To What Degree Does Loss of Skeletal Muscle with Age Contribute to Immunosenescence? https://www.fightaging.org/archives/2019/11/to-what-degree-does-loss-of-skeletal-muscle-with-age-contribute-to-immunosenescence/ Sarcopenia, the progressive loss of muscle mass and strength, is characteristic of aging. A perhaps surprisingly large fraction of the losses can be averted by strength training, but there are nonetheless inexorable process...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
We report that Werner syndrome (WS) is associated with a significant mitochondrial dysfunction, mainly manifested as defective mitophagy. This is reflected in lower NAD+ levels across species from worms to humans. NAD+ supplementation improves mitochondrial function and other age-related metabolic outcomes. Mitochondrial disease can manifest itself in multiple clinical outcomes amongst which neurodegeneration and impaired metabolism are common. Some features of WS may be explained by genomic instability due to mutation in the gene encoding the Werner protein (WRN), an important DNA helicase/exonuclease involved in DNA repa...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
More News: Alzheimer's | Biomedical Science | Brain | Genetics | Mitochondrial Disease | Neurology | Study