Autophagy and Alzheimer's Disease: From Molecular Mechanisms to Therapeutic Implications.
Md. Sahab Uddin,A. Stachowiak,Abdullah Al Mamun,Nikolay T. Tzvetkov,Shinya Takeda,Atanas G. Atanasov,Leandro Bueno Bergantin,Mohamed M. Abdel-Daim,Adrian M. Stankiewicz +8 more
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TLDR
Mechanisms and genes linking autophagy and AD, i.e., the mTOR pathway, neuroinflammation, endocannabinoid system, ATG7, BCL2, BECN1, CDK5, CLU, CTSD, FOXO1, GFAP, ITPR1, MAPT, PSEN1, SNCA, UBQLN 1, and UCHL1 are discussed.Abstract:
Alzheimer’s disease (AD) is the most common cause of progressive dementia in the elderly. It is characterized by a progressive and irreversible loss of cognitive abilities and formation of senile plaques, composed mainly of amyloid β (Aβ), and neurofibrillary tangles (NFTs), composed of tau protein, in the hippocampus and cortex of afflicted humans. In brains of AD patients the metabolism of Aβ is dysregulated, which leads to the accumulation and aggregation of Aβ. Metabolism of Aβ and tau proteins is crucially influenced by autophagy. Autophagy is a lysosome-dependent, homeostatic process, in which organelles and proteins are degraded and recycled into energy. Thus, dysfunction of autophagy is suggested to lead to the accretion of noxious proteins in the AD brain. In the present review, we describe the process of autophagy and its importance in AD. Additionally, we discuss mechanisms and genes linking autophagy and AD, i.e., the mTOR pathway, neuroinflammation, endocannabinoid system, ATG7, BCL2, BECN1, CDK5, CLU, CTSD, FOXO1, GFAP, ITPR1, MAPT, PSEN1, SNCA, UBQLN1, and UCHL1. We also present pharmacological agents acting via modulation of autophagy that may show promise in AD therapy. This review updates our knowledge on autophagy mechanisms proposing novel therapeutic targets for the treatment of AD.read more
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Amyloid Beta and Phosphorylated Tau-Induced Defective Autophagy and Mitophagy in Alzheimer’s Disease
TL;DR: How reduced levels of Drp1, Aβ, and P-Tau can enhance the clearance of damaged mitochondria and other cellular debris by autophagy and mitophagy mechanisms is discussed.
Journal ArticleDOI
APOE and Alzheimer’s Disease: Evidence Mounts that Targeting APOE4 may Combat Alzheimer’s Pathogenesis
Sahab Uddin,Tanvir Kabir,Abdullah Al Mamun,Mohamed M. Abdel-Daim,Mohamed M. Abdel-Daim,George E. Barreto,George E. Barreto,Ghulam Md Ashraf +7 more
TL;DR: ApoE has great influence in tau pathogenesis, tau-mediated neurodegeneration, and neuroinflammation, as well as α-synucleinopathy, lipid metabolism, and synaptic plasticity despite the presence of Aβ pathology.
Journal ArticleDOI
Alzheimer's Risk Factors Age, APOE Genotype, and Sex Drive Distinct Molecular Pathways.
Na Zhao,Yingxue Ren,Yu Yamazaki,Wenhui Qiao,Fuyao Li,Lindsey M. Felton,Siamak MahmoudianDehkordi,Alexandra Kueider-Paisley,Berkiye Sonoustoun,Matthias Arnold,Francis Shue,Jiaying Zheng,Olivia N. Attrebi,Yuka A. Martens,Zonghua Li,Ligia I. Bastea,Axel D. Meneses,Kai Chen,J. Will Thompson,Lisa St. John-Williams,Masaya Tachibana,Tomonori Aikawa,Hiroshi Oue,Lucy Job,Akari Yamazaki,Chia Chen Liu,Peter Storz,Yan W. Asmann,Nilufer Ertekin-Taner,Takahisa Kanekiyo,Rima Kaddurah-Daouk,Guojun Bu +31 more
TL;DR: It is found that age had the greatest impact on brain transcriptomes highlighted by an immune module led by Trem2 and Tyrobp, whereas APOE4 was associated with upregulation of multiple Serpina3 genes, and these networks and gene expression changes were mostly conserved in human brains.
Journal ArticleDOI
Therapeutic landscape for Batten disease: current treatments and future prospects.
Tyler B. Johnson,Jacob T. Cain,Katherine A. White,Denia Ramirez-Montealegre,David A. Pearce,Jill M. Weimer +5 more
TL;DR: New therapies for Batten disease are discussed, including cerliponase alfa (Brineura), the first globally approved agent, and promising new therapeutic avenues for future treatments are considered.
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