Protein aggregates and proteostasis in aging: Amylin and β-cell function. (January 2019)

• Record Type: Journal Article
• Authors: Press, Michaela; Jung, Tobias; König, Jeannette; Grune, Tilman; Höhn, Annika
• Is Part Of: Mechanisms of ageing and development. Volume 177(2019)
• Page Start: 46
• Page End: 54
• Publication Date: 2019-01
• Subjects: Aβ β-amyloid -- AD Alzheimer's disease -- ALS autophagy-lysosomal-system -- Atg autophagy-related protein -- ATP adenosin-triphosphate -- CGRP calcitonin-gene related peptide -- CMA chaperone-mediated autophagy -- DUB deubiquitinating enzyme -- EGFP enhanced green fluorescent protein -- ER endoplasmic reticulum -- IAPP islet amyloid polypeptide -- hIAPP human islet amyloid polypeptide -- Hsp heat-shock protein -- LAMP2A lysosomal associated membrane protein 2A -- LC3 microtubule-associated protein light chain 3 -- MODC mouse ornithine decarboxylase -- mTOR mechanistic target of rapamycin -- PA28 protein activator 28 -- PE phosphatidylethanolamine -- rIAPP rodent islet amyloid polypeptide -- RNS reactive nitrogen species -- ROS reactive oxygen species -- SQSTM1 sequestosome 1 -- T2D type 2 diabetes -- UCH-L1 ubiquitin carboxy-terminal hydrolase L1 -- Ub ubiquitin -- UPS ubiquitin-proteasome-system; Aging -- Proteostasis -- Protein aggregates -- Human amylin -- Proteasome -- Autophagy; Aging -- Periodicals; Developmental biology -- Periodicals; Aging -- Periodicals; Developmental Biology -- Periodicals; Vieillissement -- Périodiques; Biologie du développement -- Périodiques; Aging; Developmental biology; Periodicals; 612.67
• DOI: 10.1016/j.mad.2018.03.010
• Languages: English
• ISSNs: 0047-6374

Abstract

Graphical abstract: Highlights: Decline of proteostatic mechanisms is a characteristic of aging. Human amylin is a peptide prone to form aggregates in β-sheet conformation. Amyloidogenic human amylin seems to be involved in Type 2 Diabetes pathogenesis. Human amylin interferes with UPS and ALS leading to disturbances of proteostasis. UPS and ALS both seem to play a role in human amylin degradation. Abstract: The ubiquitin-proteasomal-system (UPS) and the autophagy-lysosomal-system (ALS) are both highly susceptible for disturbances leading to the accumulation of cellular damage. A decline of protein degradation during aging results in the formation of oxidatively damaged and aggregated proteins finally resulting in failure of cellular functionality. Besides protein aggregation in response to oxidative damage, amyloids are a different type of protein aggregates able to distract proteostasis and interfere with cellular functionality. Amyloids are clearly linked to the pathogenesis of age-related degenerative diseases such as Alzheimer's disease. Human amylin is one of the peptides forming fibrils in β-sheet conformation finally leading to amyloid formation. In contrast to rodent amylin, human amylin is prone to form amyloidogenic aggregates, proposed to play a role in the pathogenesis of Type 2 Diabetes by impairing β-cell functionality. Since aggregates such as lipofuscin and β-amyloid are known to impair proteostasis, it is likely to assume similar effects for human amylin. In this review, we focus on the effects of IAPP on UPS and ALS and their role in amylin degradation, since both systems play a crucial role in maintaining proteome balance thereby influencing, at least in part, cellular fate and aging.