Table 1.

Proteins affecting proteostasis in Alzheimer’s disease

Protein	Function	Reference
Aβ40/42	Decreases proteasome activity, modulates autophagy through mTOR signaling	[99–102, 104, 143–146]
Tau	Inhibitory effect of Tau aggregates on proteasome activity	[115]
HSF1	Induces APP gene during stress	[81, 82]
GRP78 (ER isoform of HSP70)	Modulates APP maturation and reduces Aβ40/42 secretion	[84, 85]
HSPs (HSP22, 27, 70, 90)	Small HSPs (HSP22, HSP27) bind to fibrillar amyloid plaques and inhibit their fibrillarisation; HSP70, HSP90 inhibit early stages of amyloid aggregation	[88, 89]
CHIP	E3 enzyme for phosphorylated Tau	[93, 117]
BAG1	Regulates proteasomal degradation of Tau together with HSP70	[97]
PS1	Increases production of Aβ42, essential for lysosomal proteolysis and autophagy by enabling the acidification of lysosomes required for protease activation	[163, 165]
UBB+1	Potently inhibits the degradation of polyubiquitinated substrates and therefore induces neuronal cell death	[120, 121]
UCH-L1	DUB needed for proteasomal degradation of client proteins, oxidized and down-regulated in AD	[124, 125]
UBQLN1	UBQLN1 activity is necessary to regulate the production of APP and APP fragments	[127, 128]
mTOR	Inhibitory and/or activating modulation of mTOR through Aβ42 but not Aβ40	[143–146]
BECLIN1	BECLIN1 is down-regulated in AD brains and consequently increases APP levels and its metabolites	[161, 162]

Aβ amyloid beta, APP amyloid precursor protein, HSF1 heat shock transcription factor 1, GRP78 glucose-related protein 78, HSP heat shock protein, CHIP carboxy terminus of HSC70-interacting protein, BAG1 BCL2-associated athanogene 1, PS1 Presenilin 1, UCH-L1 ubiquitin carboxy terminal hydrolase isozyme 1, UBQLN1 Ubiquilin 1, mTOR mammalian target of rapamycin, DUB deubiquitination enzyme, ER endoplasmic reticulum