scholarly journals GSK-3β-induced Tau pathology drives hippocampal neuronal cell death in Huntington’s disease: involvement of astrocyte–neuron interactions

2016 ◽  
Vol 7 (4) ◽  
pp. e2206-e2206 ◽  
Author(s):  
F L'Episcopo ◽  
J Drouin-Ouellet ◽  
C Tirolo ◽  
A Pulvirenti ◽  
R Giugno ◽  
...  
Keyword(s):  
Cell Death ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Tau Pathology ◽  
Neuron Interactions ◽  
Gsk 3Β

Mechanisms of neuronal cell death in Huntington’s disease

2003 ◽  
Vol 100 (1-4) ◽  
pp. 287-295 ◽  
Author(s):  
A. Sawa ◽  
T. Tomoda ◽  
B.-I. Bae
Keyword(s):  
Cell Death ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neuronal Cell Death ◽  
Neuronal Cell

scholarly journals Delta-secretase-cleaved Tau antagonizes TrkB neurotrophic signalings, mediating Alzheimer’s disease pathologies

2019 ◽  
Vol 116 (18) ◽  
pp. 9094-9102 ◽  
Author(s):  
Jie Xiang ◽  
Zhi-Hao Wang ◽  
Eun Hee Ahn ◽  
Xia Liu ◽  
Shan-Ping Yu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Death ◽  
Molecular Mechanisms ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Trophic Factor ◽  
Tau Pathology ◽  
Trkb Receptors ◽  
Repeat Domain

BDNF, an essential trophic factor implicated in synaptic plasticity and neuronal survival, is reduced in Alzheimer’s disease (AD). BDNF deficiency’s association with Tau pathology in AD is well documented. However, the molecular mechanisms accounting for these events remain incompletely understood. Here we show that BDNF deprivation triggers Tau proteolytic cleavage by activating δ-secretase [i.e., asparagine endopeptidase (AEP)], and the resultant Tau N368 fragment binds TrkB receptors and blocks its neurotrophic signals, inducing neuronal cell death. Knockout of BDNF or TrkB receptors provokes δ-secretase activation via reducing T322 phosphorylation by Akt and subsequent Tau N368 cleavage, inducing AD-like pathology and cognitive dysfunction, which can be restored by expression of uncleavable Tau N255A/N368A mutant. Blocking the Tau N368–TrkB complex using Tau repeat-domain 1 peptide reverses this pathology. Thus, our findings support that BDNF reduction mediates Tau pathology via activating δ-secretase in AD.

scholarly journals Recent Trends in Detection of Huntingtin and Preclinical Models of Huntington’s Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Neelima Mantha ◽  
Nandita G. Das ◽  
Sudip K. Das
Keyword(s):  
Molecular Biology ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Animal Species ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Preclinical Models ◽  
Recent Trends ◽  
The Brain ◽  
Preclinical Screening

Huntington’s disease is a genetically inherited neurodegenerative disease that is characterized by neuronal cell death in the brain. Molecular biology techniques to detect and quantify huntingtin protein in biological samples involve fluorescence imaging, western blotting, and PCR. Modified cell lines are widely used as models for Huntington’s disease for preclinical screening of drugs to study their ability to suppress the expression of huntingtin. Although worm and fly species have been experimented on as models for Huntington’s disease, the most successful animal models have been reported to be primates. This review critically analyses the molecular biology techniques for detection and quantitation of huntingtin and evaluates the various animal species for use as models for Huntington’s disease.

scholarly journals Involvment of Cytosolic and Mitochondrial GSK-3β in Mitochondrial Dysfunction and Neuronal Cell Death of MPTP/MPP+-Treated Neurons

PLoS ONE ◽  
2009 ◽  
Vol 4 (5) ◽  
pp. e5491 ◽  
Author(s):  
Agnès Petit-Paitel ◽  
Frédéric Brau ◽  
Julie Cazareth ◽  
Joëlle Chabry
Keyword(s):  
Cell Death ◽  
Mitochondrial Dysfunction ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Gsk 3Β

Role of GSK-3β activity in motor neuronal cell death induced by G93A or A4V mutant hSOD1 gene

2005 ◽  
Vol 22 (2) ◽  
pp. 301-309 ◽  
Author(s):  
Seong-Ho Koh ◽  
Young-Bae Lee ◽  
Kyung S. Kim ◽  
Hyun-Jung Kim ◽  
Manho Kim ◽  
...  
Keyword(s):  
Cell Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Gsk 3Β

scholarly journals Potential application of grape derived polyphenols in Huntington’s disease

2010 ◽  
Vol 1 (2) ◽  
Author(s):  
Jun Wang ◽  
Cathie Pfleger ◽  
Lauren Friedman ◽  
Roselle Vittorino ◽  
Wei Zhao ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neurodegenerative Disorder ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Feasibility Studies ◽  
Grape Seed ◽  
Polyphenolic Extract

AbstractHuntington’s disease (HD) is a progressive neurodegenerative disorder associated with selective neuronal cell death. Abnormal aggregation of huntingtin protein with polyQ expansion has been shown to be causally linked to HD. Grape seed polyphenolic extract (GSPE) is a natural compound that has previously been shown to interfere with aggregations of proteins involved in neurological disorders, such as amyloid beta peptides (Aβ) and Tau protein. In this study we found that GSPE treatment significantly inhibits polyQ aggregation in phaeochromocytoma (PC)-12 cell line containing an ecdysone-inducible protein comprising the first 17 amino acid of huntingtin plus 103 glutamines fused with enhanced GFP. In vivo feasibility studies using the Q93httexon1 drosophila model of HD, we extended our in vitro evidence and found that flies fed with GSPE had a significantly improved lifespan compared to the control flies. Using the R6/2 rodent model of HD, we found that oral administration of 100 mg/kg/day GSPE (equivalent to 500mg per day in human) significantly attenuated the motor skill decay as well as extended the lifespan in the R6/2 mice relative to vehicle-control mice. Collectively, our studies strongly suggest that GSPE might be able to modulate the onset and/or progression of HD.

scholarly journals Resveratrol modulates the Akt/GSK-3β signaling pathway in a middle cerebral artery occlusion animal model

2019 ◽  
Vol 35 (1) ◽  
Author(s):  
Dong-Ju Park ◽  
Ju-Bin Kang ◽  
Fawad-Ali Shah ◽  
Phil-Ok Koh
Keyword(s):  
Cell Death ◽  
Cerebral Ischemia ◽  
Middle Cerebral Artery ◽  
Signaling Pathway ◽  
Neuroprotective Effect ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Artery Occlusion ◽  
Gsk 3Β ◽  
Cerebral Artery Occlusion

Abstract Cerebral ischemia is a major cause of neurodegenerative disease. It induces neuronal vulnerability and susceptibility, and leads to neuronal cell death. Resveratrol is a polyphenolic compound that acts as an anti-oxidant. It exerts a neuroprotective effect against focal cerebral ischemic injury. Akt signaling pathway is accepted as a representative cell survival pathway, including proliferation, growth, and glycogen synthesis. This study investigated whether resveratrol regulates Akt/glycogen synthase kinase-3β (GSK-3β) pathway in a middle cerebral artery occlusion (MCAO)-induced ischemic brain injury. Adult male rats were intraperitoneally injected with vehicle or resveratrol (30 mg/kg) and cerebral cortices were isolated 24 h after MCAO. Neurological behavior test, corner test, brain edema measurment, and 2,3,5-triphenyltetrazolium chloride staining were performed to elucidate the neuroprotective effects of resveratrol. Phospho-Akt and phospho-GSK-3β expression levels were measured using Western blot analysis. MCAO injury led to severe neurobehavioral deficit, infraction, and histopathological changes in cerebral cortex. However, resveratrol treatment alleviated these changes caused by MCAO injury. Moreover, MCAO injury induced decreases in phospho-Akt and phospho-GSK-3β protein levels, whereas resveratrol attenuated these decreases. Phosphorylations of Akt and GSK-3β act as a critical role for the suppression of apoptotic cell death. Thus, our finding suggests that resveratrol attenuates neuronal cell death in MCAO-induced cerebral ischemia and Akt/GSK-3β signaling pathway contributes to the neuroprotective effect of resveratrol.

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