tau Proteins

Publication Title: 
Human Molecular Genetics

Niemann-Pick type C (NPC) disease, an autosomal recessive disorder caused primarily by loss-of-function mutations in NPC1 gene, is characterized neuropathologically by intracellular cholesterol accumulation, gliosis and neuronal loss in selected brain regions. Recent studies have shown that NPC disease exhibits intriguing parallels with Alzheimer's disease (AD), including the presence of tau-positive neurofibrillary tangles (NFTs) and ?-amyloid (A?)-related peptides in vulnerable brain regions. Since enhanced cholesterol level, which acts as a risk factor for AD, can increase A?

Author(s): 
Maulik, Mahua
Ghoshal, Bibaswan
Kim, John
Wang, Yanlin
Yang, Jing
Westaway, David
Kar, Satyabrata
Publication Title: 
Aging Cell

Accumulation of tau is a critical event in several neurodegenerative disorders, collectively known as tauopathies, which include Alzheimer's disease and frontotemporal dementia. Pathological tau is hyperphosphorylated and aggregates to form neurofibrillary tangles. The molecular mechanisms leading to tau accumulation remain unclear and more needs to be done to elucidate them. Age is a major risk factor for all tauopathies, suggesting that molecular changes contributing to the aging process may facilitate tau accumulation and represent common mechanisms across different tauopathies.

Author(s): 
Caccamo, Antonella
MagrÏ, Andrea
Medina, David X.
Wisely, Elena V.
LÛpez-Aranda, Manuel F.
Silva, Alcino J.
Oddo, Salvatore
Publication Title: 
Journal of Cell Science

Protein with tau-like repeats (PTL-1) is the sole Caenorhabditis elegans homolog of tau and MAP2, which are members of the mammalian family of microtubule-associated proteins (MAPs). In mammalian neurons, tau and MAP2 are segregated, with tau being mainly localised to the axon and MAP2 mainly to the dendrite. In particular, tau plays a crucial role in pathology, as elevated levels lead to the formation of tau aggregates in many neurodegenerative conditions including Alzheimer's disease. We used PTL-1 in C.

Author(s): 
Chew, Yee Lian
Fan, Xiaochen
Gˆtz, J¸rgen
Nicholas, Hannah R.
Publication Title: 
Biochemical Pharmacology

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. With an increasing longevity and the absence of a cure, AD has become not only a major health problem but also a heavy social and economic burden worldwide. In addition to the presence of abundant intra- and extra-cellular neurotoxic amyloid ? (A?) peptides, which form the amyloid plaques, and intracellular hyperphosphorylated tau protein, the main component of neurofibrillary tangles, consistent evidence indicates that the AD brain is characterized by extensive neuroinflammatory processes.

Author(s): 
Giannopoulos, Phillip F.
Joshi, Yash B.
PraticÚ, Domenico
Publication Title: 
Journal of Neuroscience Research

Fundamental questions on the pathogenesis of Alzheimer's disease (AD) are how nontoxic, soluble amyloid beta-protein (A beta) is converted to its toxic, aggregated form and how functional tau is hyperphosphorylated to form neurofibrillary tangles. Growing evidence from recent biochemical and cell biological studies suggests that altered cholesterol metabolism in neurons may underlie such pathological processes. The possibility that cholesterol is a risk factor in the development of AD has also been supported by recent epidemiological studies.

Author(s): 
Yanagisawa, Katsuhiko
Publication Title: 
Aging Cell

In laboratory animals, calorie restriction (CR) protects against aging, oxidative stress, and neurodegenerative pathologies. Reduced levels of growth hormone and IGF-1, which mediate some of the protective effects of CR, can also extend longevity and/or protect against age-related diseases in rodents and humans. However, severely restricted diets are difficult to maintain and are associated with chronically low weight and other major side effects.

Author(s): 
Parrella, Edoardo
Maxim, Tom
Maialetti, Francesca
Zhang, Lu
Wan, Junxiang
Wei, Min
Cohen, Pinchas
Fontana, Luigi
Longo, Valter D.
Publication Title: 
Journal of Neurology, Neurosurgery, and Psychiatry

The genetic analysis of common neurological disorders will be a difficult and protracted endeavour. Genetics is only one of many disciplines that will be required but it has already thrown considerable light on the aetiology of several major neurological disorders through the analysis of rare inherited subgroups. The identification of individual susceptibility genes with variants of smaller effect will be more difficult but there is no sharp demarcation between large and small genetic effects, so that many new and important insights will emerge using existing and new technologies.

Author(s): 
Wright, A. F.
Publication Title: 
PLoS genetics

Little is known about how changes in DNA methylation mediate risk for human diseases including dementia. Analysis of genome-wide methylation patterns in patients with two forms of tau-related dementia--progressive supranuclear palsy (PSP) and frontotemporal dementia (FTD)--revealed significant differentially methylated probes (DMPs) in patients versus unaffected controls. Remarkably, DMPs in PSP were clustered within the 17q21.31 region, previously known to harbor the major genetic risk factor for PSP.

Author(s): 
Li, Yun
Chen, Jason A.
Sears, Renee L.
Gao, Fuying
Klein, Eric D.
Karydas, Anna
Geschwind, Michael D.
Rosen, Howard J.
Boxer, Adam L.
Guo, Weilong
Pellegrini, Matteo
Horvath, Steve
Miller, Bruce L.
Geschwind, Daniel H.
Coppola, Giovanni
Publication Title: 
PloS One

The miRBase-21 database currently lists 1881 microRNA (miRNA) precursors and 2585 unique mature human miRNAs. Since their discovery, miRNAs have proved to present a new level of epigenetic post-transcriptional control of protein synthesis. Initial results point to a possible involvement of miRNA in Alzheimer's disease (AD). We applied OpenArray technology to profile the expression of 1178 unique miRNAs in cerebrospinal fluid (CSF) samples of AD patients (n = 22) and controls (n = 28).

Author(s): 
Denk, Johannes
Boelmans, Kai
Siegismund, Christine
Lassner, Dirk
Arlt, Sˆnke
Jahn, Holger
Publication Title: 
Current Alzheimer Research

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by amyloid-? (A?) plaque formation, tau pathology, neurodegeneration and inflammatory processes. Monocytes are involved in inflammation in AD and are recruited to the diseased brain. Recently it has been shown that aberrant epigenetic processes including acetylation are associated with the development of AD.

Author(s): 
Plagg, Barbara
Ehrlich, Daniela
Kniewallner, Kathrin M.
Marksteiner, Josef
Humpel, Christian

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