Role of Protein Misfolding and Proteostasis Deficiency in Protein Misfolding Diseases and Aging

Table 1

Genetic modulation of proteasome in different models and its effect on aging and disease.

Subunit deficiency/overexpression	Function	Phenotype	Model	Reference
Rpt2 inactivation	ATPase	Ubiquitin and 𝛼-synuclein positive Lewy like intraneural inclusion in neurons and neurodegeneration	Mus musculus	[59]
Rpt3 inactivation	ATPase	TDP43, FUS accumulation, basophilic inclusion bodies in neurons, locomotor impairment, loss of neurons	Mus musculus	[60]
𝛽5t deletion	Chymotrypsin-like proteolytic activity	Shortening of lifespan, accumulation of polyubiquitinated and oxidized proteins, aggravated age-related metabolic disorder	Mus musculus	[66]
Rpn11 overexpression	Deubiquitination of the proteasome; substrate	Extension of lifespan, suppression of polyQ induced toxicity	Drosophila melanogaster	[15]
Rpn6 overexpression	Stabilizing the interaction between CP and RP	Extension of lifespan under mild stress condition	Caenorhabditis elegans	[16]