ALS and FTD: an epigenetic perspective.

Area of Science:

• Neuroscience
• Genetics
• Epigenetics

Background:

• Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are fatal neurodegenerative diseases with up to 50% comorbidity.
• Despite extensive research, effective biomarkers and therapeutics for neuronal death in ALS and FTD remain elusive.
• The C9orf72 hexanucleotide repeat expansion highlights novel pathogenic pathways, including chromatin remodeling and transcriptome alteration.

Purpose of the Study:

• To review current knowledge on altered epigenetic processes in ALS and FTD.
• To discuss potential therapeutic strategies targeting epigenetic mechanisms in these diseases.
• To highlight the potential of epigenetics in explaining genetically unexplained sporadic cases.

Main Methods:

• Review of existing literature on epigenetic alterations in ALS and FTD.
• Analysis of the role of DNA methylation, histone modifications, and RNA editing.
• Discussion of emerging therapeutic strategies targeting epigenetic pathways.

Main Results:

• Epigenetic processes regulate key cellular functions including DNA replication, repair, RNA transcription, and chromatin conformation.
• Alterations in DNA methylation and histone modification have been reported in ALS and FTD, though research is in early stages.
• The epigenome's responsiveness to aging and environmental signals suggests a central role in ALS and FTD pathogenesis, especially in sporadic forms.

Conclusions:

• Epigenetic mechanisms are increasingly recognized as critical players in the pathogenesis of ALS and FTD.
• Targeting epigenetic processes presents a promising therapeutic strategy, particularly for the majority of genetically unexplained cases.
• Further evaluation of multiple epigenetic players is necessary to fully understand and treat these devastating diseases.