PROTEOSTASIS (Protein Homeostasis) is the maintenane of homeostasis for protein production, maintenance and removal in the body. When an organism maintains proteostasis, cells remain healthy, disease is inhibited, tissue aging is slowed, and an longevity is extended. Mechanism involved in proteostasis include autophagy, protein synthesis and degradation. Proteostasis is an essential element for extending the lifespan.
Nrf2 - Transcription factor for regulating proteostasis. Nrf2 plays a central role in proteostasis by activating genes supporting the endoplasmic recticulum (the cellular organelle involved in protein synthesis), the proteasome (complex used for degrading damaged proteins) and autophagy.(1)
Glycogen synthase kinase 3β (GSK-3β) Inhibition - Involved in formation of amyloid plaques - the acculmulation of dysfunctional amyloid proteins. GSK inhibits Nrf2, thereby disrupting proteostasis.(2) Inhibiting GSK is considered a theraputic approach to Alzheimers Disease.
Lipofuscin - Cellular waste products, SIgn of Aging.
REFERENCES:
(1) Pajares M, et al. Modulation of proteostasis by transcription factor NRF2 and impact in neurodegenerative diseases. Redox Biol. 2017 Apr;
(2) Robledinos-Anton N, et al. Activators and Inhibitors of NRF2: A Review of Their Potential for Clinical Development. Oxid Med Cell Longev. 2019
(3) Paudel P, et al. Rosmarinic Acid Derivatives' Inhibition of Glycogen Synthase Kinase-3β Is the Pharmacological Basis of Kangen-Karyu in Alzheimer's Disease. Molecules. 2018 Nov