Proteinopathies associated to repeat expansion disorders.

Area of Science:

• Neuroscience
• Genetics
• Molecular Biology

Background:

• Neurodegenerative diseases (e.g., Alzheimer's, Parkinson's) involve synaptic dysfunction, neuronal loss, and protein aggregates (proteinopathies).
• Other neurodegenerative conditions, such as Huntington's disease and C9ORF72-associated frontotemporal dementia/amyotrophic lateral sclerosis, stem from genetic repeat expansion disorders.

Purpose of the Study:

• To describe the molecular nature and location of expanded DNA tracts in repeat expansion disorders.
• To elucidate the consequences of these expanded tracts on clinical phenotypes.
• To detail the pathomechanisms linking repeat expansions to proteinopathies.

Main Methods:

• Review of molecular alterations at DNA, RNA, and protein levels.
• Analysis of loss-of-function (LOF) and gain-of-function (GOF) mechanisms.
• Focus on protein misfolding, polymerization, and aggregation.

Main Results:

• Expanded DNA tracts trigger molecular changes leading to proteinopathies.
• Distinct pathomechanisms (LOF, GOF) are associated with repeat expansions.
• Understanding these mechanisms is crucial for therapeutic development.

Conclusions:

• Repeat expansion disorders contribute to specific proteinopathies through defined molecular pathways.
• Advances in understanding these mechanisms are paving the way for innovative therapeutic strategies.
• Biomarkers associated with these pathways are emerging.