Protein aggregates and proteostasis in aging: Amylin and β-cell function

Area of Science:

• Cellular Biology
• Aging Research
• Biochemistry

Background:

• Protein degradation systems, including the ubiquitin-proteasomal-system (UPS) and autophagy-lysosomal-system (ALS), are crucial for cellular health.
• Aging is associated with impaired protein degradation, leading to the accumulation of damaged and aggregated proteins.
• Amyloidogenic proteins, such as human amylin, are implicated in age-related diseases and can disrupt cellular proteostasis.

Purpose of the Study:

• To review the impact of human amylin (Islet amyloid polypeptide - IAPP) on the UPS and ALS.
• To explore the role of these degradation systems in amylin degradation.
• To understand how IAPP-induced proteostasis disruption contributes to cellular dysfunction and aging.

Main Methods:

• Literature review focusing on the interplay between IAPP, UPS, and ALS.
• Analysis of studies investigating protein aggregation and degradation pathways.
• Synthesis of current knowledge on the mechanisms of amylin-induced cellular damage.

Main Results:

• Human amylin forms amyloidogenic aggregates that can impair cellular function.
• Both UPS and ALS are involved in the degradation of protein aggregates.
• Dysfunction of UPS and ALS can exacerbate the effects of amylin aggregation, contributing to cellular damage.

Conclusions:

• Human amylin aggregation poses a significant threat to proteostasis.
• The efficiency of UPS and ALS in degrading amylin aggregates is critical for maintaining cellular health.
• Impaired protein degradation pathways, exacerbated by amylin, likely contribute to cellular aging and disease pathogenesis.