We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Amyloids: Regulators of Metal Homeostasis in the Synapse.
- Authors
Kawahara, Masahiro; Kato-Negishi, Midori; Tanaka, Ken-ichiro; Penke, Botond; Rosa, Carmelo La
- Abstract
Conformational changes in amyloidogenic proteins, such as β-amyloid protein, prion proteins, and α-synuclein, play a critical role in the pathogenesis of numerous neurodegenerative diseases, including Alzheimer's disease, prion disease, and Lewy body disease. The disease-associated proteins possess several common characteristics, including the ability to form amyloid oligomers with β-pleated sheet structure, as well as cytotoxicity, although they differ in amino acid sequence. Interestingly, these amyloidogenic proteins all possess the ability to bind trace metals, can regulate metal homeostasis, and are co-localized at the synapse, where metals are abundantly present. In this review, we discuss the physiological roles of these amyloidogenic proteins in metal homeostasis, and we propose hypothetical models of their pathogenetic role in the neurodegenerative process as the loss of normal metal regulatory functions of amyloidogenic proteins. Notably, these amyloidogenic proteins have the capacity to form Ca2+-permeable pores in membranes, suggestive of a toxic gain of function. Therefore, we focus on their potential role in the disruption of Ca2+ homeostasis in amyloid-associated neurodegenerative diseases.
- Subjects
AMINO acid sequence; TRACE metals; METALS; PRION diseases; SYNAPSES; HOMEOSTASIS
- Publication
Molecules, 2020, Vol 25, Issue 6, p1441
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules25061441