Genomic Instability and Neurodegeneration

Genomic instability can be defined as an increased probability in accumulating genome damage, acquired either through a defect in the repair of such damage, or an accumulation of inductive triggers. While genomic instability is a well-established hallmark of cancer and aging, its relevance for neurodegeneration remains less well understood. This is about to change as we begin to recognize that age is intrinsically linked to the most frequent neurodegenerative diseases, and that neurons due to their particular metabolism and their non-dividing state, are particularly prone to accumulate DNA damage. It is thus crucial to investigate the origins of genomic instability in neurons, how this instability might trigger neurodegeneration and to identify possible targets for intervention.

The goal of this research topic is to assemble a global picture of the different origins of genomic instability in neurodegeneration, the downstream pathways involved and an evaluation of the potential for therapeutic intervention.

We are interested in receiving all article types addressing the following specific themes:

(1) Which are the origins of genomic instability in neurons?
• natural or accelerated aging; oxidative stress, genetic risk factors, DNA repair deficiencies, epigenetic dysregulation.
• genome instability syndromes and neurodegeneration.
• LINE-1 retrotransposons.
• neuronal activity.
• mitochondrial deficiencies.
• topological constraints during transcription.
• R-loop formation.
• RNA splicing alterations.

(2) What happens downstream of genomic instability in neurons?

(3) Which could be anchor points to target therapeutic interventions on the basis of (1) and (2).

Topic Editor Dr Julia Fuchs is a co-author in multiples patents related to genomic modifications. All other Topic Editors declare no competing interests with regards to the Research Topic subject.