Table 1 The physiological roles of AD-related DUBs.

DUB	Disease relevance	Functions	Refs.
DUBs regulate Aβ
USP8	Upregulated	Reduces K501 ubiquitination of BACE1	[35]
USP25	Upregulated	Rescues the degradation of APP	[42]
USP46	Downregulated	Reverses Aβ-dependent AMPAR ubiquitination	[34, 45]
DUBs regulate Tau
USP9 X	Upregulated	Regulates of phosphorylation and expression of Tau	[24, 25]
USP9 Y	Downregulated	Regulates of phosphorylation and expression of Tau	[24, 25]
OTUB1	Upregulated	Removes the K48 polyubiquitin chain from Tau	[26]
USP14	Upregulated	Inhibits the degradation of Tau by 26S proteasome	[56, 58]
USP10	Upregulated	Binds and deubiquitinates Tau	[61]
USP11	Upregulated	Deubiquitinates Tau at K281	[63]
DUBs regulate Aβ and Tau
UCH-L1/3/5	Downregulated	Controls the degradation of APP, BACE1, and Tau	[67, 68, 71]
USP13	Upregulated	Deubiquitinates parkin and Tau	[87, 89, 157]

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