1.

Pathogenic protein misfolding

Causes/factors	Misfolded protein/disease	Reference
Nature of the protein: (ageing, Hydrophobicity)	Ageing: transthyretin protein in senile systematic amyloidoses Hydrophobicity: Aβ, Prion proteins,	[35][36][37]
Concentration dependence	Aβ in Alzheimer's disease (AD)	[38]
Mutations in amino acid sequences in the protein	Hereditary amyloidosis APP in AD	[39][4] see Table 2
Mutations in associating proteins	β2-Microglobulin mutations	[40]
Chemical modifications of the protein	Protonation of AfS Oxidative modifications of Aβ	[2][41][42]
Protein folding machinery (Chaperones, heat shock proteins)	Aβ in AD Alpha synuclein in Parkinson disease	[43][44]
Altered proteolysis or turnover of precursor protein	Mutations in Amyloid precursor protein in AD Presenilin mutations in AD	[4,5][45,46]
Decreased clearance	Aβ in AD Alpha synuclein in Parkinson disease	[47][48]
Time of incubation	Aβ in AD	[49]
Temperature and ionic strength	Aβ in AD	[50]
Local interacting factors (other proteins, metals, osmolytes)	Aβ and Metals Osmolytes and prions ApoE and AfS	[51], [52], [53][47,54,55]