Protein Misfolding and Aggregation: The Relatedness between Parkinson's Disease and Hepatic Endoplasmic Reticulum...

Area of Science:

• Molecular Biology
• Neuroscience
• Genetics

Background:

• Cellular homeostasis dysfunction leads to protein misfolding and pathological aggregation.
• This process is implicated in neurodegenerative diseases like Parkinson's disease (PD) and endoplasmic reticulum storage disorders (ERSDs), including alpha-1-antitrypsin deficiency (AATD) and hereditary hypofibrinogenemia with hepatic storage (HHHS).

Purpose of the Study:

• To review the pathological basis of protein misfolding and aggregation in PD, AATD, and HHHS.
• To examine the link between protein aggregation and endoplasmic reticulum (ER) stress in these diseases.
• To compare proteostasis and homeostasis regulation mechanisms and explore potential common therapeutic strategies.

Main Methods:

• Literature review of pathological mechanisms.
• Analysis of protein aggregation in alpha-synuclein (PD), alpha-1-antitrypsin (AATD), and fibrinogen (HHHS).
• Comparison of ER stress responses, unfolded protein response, and autophagy.

Main Results:

• Identified shared pathophysiological pathways in protein misfolding and aggregation across diverse diseases.
• Highlighted the role of ER stress and proteostasis dysfunction in PD, AATD, and HHHS.
• Demonstrated similarities in cellular defense mechanisms like the unfolded protein response and autophagy.

Conclusions:

• Despite varied symptoms, PD and ERSDs share underlying mechanisms of protein misfolding and aggregation.
• Targeting these common pathways, particularly ER stress and proteostasis, offers potential for novel, shared therapeutic approaches.