Histone Post-Translational Modifications and DNA Double-Strand Break Repair in Neurodegenerative Diseases: An...

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Neurons accumulate metabolic and oxidative damage over a lifetime.
• DNA double-strand breaks (DSBs) are repaired via homologous recombination (HR) or non-homologous end joining (NHEJ).
• Post-mitotic neurons have limited HR capacity, making them vulnerable to DNA damage and repair defects.

Purpose of the Study:

• To review histone post-translational modification (PTM) alterations in neurodegenerative diseases.
• To highlight histone PTMs as potential therapeutic targets for neurodegeneration.
• To explore the link between DNA damage, histone PTMs, and neuronal decay.

Main Methods:

• Literature review of histone PTM alterations in neurodegenerative diseases.
• Analysis of the role of histone PTMs in DNA double-strand break (DSB) repair.
• Examination of the DNA damage response (DDR) in the context of neurodegeneration.

Main Results:

• Histone PTM alterations are observed in Amyotrophic Lateral Sclerosis/Frontotemporal Dementia, Parkinson's Disease, Alzheimer's Disease, Multiple Sclerosis, and Huntington's Disease.
• Aberrant histone PTMs can facilitate an abnormal DNA damage response (DDR).
• This aberrant DDR contributes to the progression of neurodegeneration.

Conclusions:

• Histone PTMs play a critical role in regulating DNA damage repair in neurons.
• Altered histone PTMs contribute to neurodegeneration by enabling an aberrant DDR.
• Targeting histone PTMs may offer novel therapeutic strategies to mitigate neurodegeneration and promote neuronal survival.