Journal ArticleDOI
Alzheimer's Disease: Genes, Proteins, and Therapy
TLDR
Evidence that the presenilin proteins, mutations in which cause the most aggressive form of inherited AD, lead to altered intramembranous cleavage of the beta-amyloid precursor protein by the protease called gamma-secretase has spurred progress toward novel therapeutics and provided discrete biochemical targets for drug screening and development.Abstract:
Rapid progress in deciphering the biological mechanism of Alzheimer's disease (AD) has arisen from the application of molecular and cell biology to this complex disorder of the limbic and association cortices. In turn, new insights into fundamental aspects of protein biology have resulted from research on the disease. This beneficial interplay between basic and applied cell biology is well illustrated by advances in understanding the genotype-to-phenotype relationships of familial Alzheimer's disease. All four genes definitively linked to inherited forms of the disease to date have been shown to increase the production and/or deposition of amyloid β-protein in the brain. In particular, evidence that the presenilin proteins, mutations in which cause the most aggressive form of inherited AD, lead to altered intramembranous cleavage of the β-amyloid precursor protein by the protease called γ-secretase has spurred progress toward novel therapeutics. The finding that presenilin itself may be the long-sought γ-...read more
Citations
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Unfolded proteins and endoplasmic reticulum stress in neurodegenerative disorders
TL;DR: The IRE1 axis: non‐conventional splicing of XBP1 mRNA and the PERK axis: attenuation of translation and the ATF6 axis: regulated proteolytic activation are studied.
Journal ArticleDOI
Cerebral Amyloid Angiopathy: A Systematic Review
TL;DR: A systematic review of existing evidence regarding the epidemiology, genetics, pathogenesis, diagnosis and clinical management of cerebral amyloid angiopathy is presented.
Journal ArticleDOI
ER stress in Alzheimer's disease: a novel neuronal trigger for inflammation and Alzheimer's pathology
TL;DR: The mechanisms which could link the ER stress of neurons to the activation of the inflammatory response and the evolution of pathological changes in AD are described.
Journal ArticleDOI
Deciphering the genetic basis of Alzheimer's disease
TL;DR: Understanding of the genotype-to-phenotype conversions of familial AD has led to the development of pharmacological strategies to lower amyloid beta-protein levels as a way of treating or preventing all forms of the disease.
Journal ArticleDOI
Mitochondrial dysfunction, apoptotic cell death, and Alzheimer's disease.
Anne Eckert,Uta Keil,Celio A. Marques,Astrid Bonert,Claudia Frey,Katrin Schüssel,Walter E. Müller +6 more
TL;DR: A hypothetical sequence of the pathogenic steps linking sporadic AD, FAD, and Abeta production with mitochondrial dysfunction, caspase pathway, and neuronal loss is emphasized.
References
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Journal ArticleDOI
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Journal ArticleDOI
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Journal ArticleDOI
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