C9orf72 poly(PR) mediated neurodegeneration is associated with nucleolar stress

• Published in: bioRxiv
• Main Authors: Cicardi, Maria Elena, Hallgren, Justin, Darilang, Mawrie, Krishnamurthy, Karthik, Shashirekha Shamamandri Markandaiah, Nelson, Andrew T, Kankate, Vaishnavi, Anderson, Eric, Pasinelli, Piera, Udai Bhan Pandey, Eischen, Christine M, Trotti, Davide
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 16.02.2023
• Subjects: Amyotrophic lateral sclerosis; Apoptosis; Caspase-3; Cellular stress response; Frontotemporal dementia; Neurodegeneration; Neurotoxicity; Nucleoli; p53 Protein; Phenotypes; Senescence

The ALS/FTD-linked intronic hexanucleotide repeat expansion in the C9orf72 gene is translated into dipeptide repeat proteins, among which poly-proline-arginine (PR) displays the most aggressive neurotoxicity in-vitro and in-vivo. PR partitions to the nucleus when expressed in neurons and other cell...