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Amyloids: Regulators of Metal Homeostasis in the Synapse
- Source :
- Molecules, Molecules, Vol 25, Iss 6, p 1441 (2020)
- Publication Year :
- 2020
- Publisher :
- MDPI, 2020.
-
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 :
- Amyloid
channel
Pharmaceutical Science
Amyloidogenic Proteins
Review
Analytical Chemistry
lcsh:QD241-441
Pathogenesis
Synapse
03 medical and health sciences
0302 clinical medicine
lcsh:Organic chemistry
Drug Discovery
neurotoxicity
Sheet structure
medicine
Humans
Physical and Theoretical Chemistry
Cytotoxicity
Peptide sequence
030304 developmental biology
0303 health sciences
calcium
Ion Transport
Chemistry
Organic Chemistry
zinc
Neurotoxicity
Neurodegenerative Diseases
medicine.disease
Cell biology
Trace Elements
Chemistry (miscellaneous)
copper
Synapses
Molecular Medicine
030217 neurology & neurosurgery
Homeostasis
Subjects
Details
- Language :
- English
- ISSN :
- 14203049
- Volume :
- 25
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Molecules
- Accession number :
- edsair.doi.dedup.....7e0d30d14f3c089fcb375a2174464003