Discovered the lack of a protein in the neurons of patients with neurodegenerative diseases. « Medicine in the Library

DP-43 it is an RNA-binding protein that normally resides in the nucleus of neurons but is abnormally localized in the cytoplasm of neurons in most patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, and up to half of patients with Alzheimer’s disease.

The researchers of the Massachusetts General Hospital (MGH)had previously shown that loss of nuclear TDP-43 leads to abnormalities in the RNA encoding a protein essential for the ability of neurons to regenerate their axons after injury and to maintain their connection with muscles to control movement .

The protein that the researchers found to be most affected by TDP-43 is called stathmin-2. The absence of nuclear TDP-43 leads to abnormal processing of stathmin-2 RNA, resulting in elevated levels of a non-functioning truncated stathmin-2 RNA and marked loss of stathmin-2 protein in neurons.

“Stathmin-2 discontinuation is a prominent abnormality observed in patients with a spectrum of neurodegenerative diseases, including nearly all cases of sporadic and familial ALS, as well as a large proportion of patients with dementiasays Clotilde Lagier-Tourenne, MD, PhD, an associate professor of neurology at MGH and Harvard Medical School.

The team also identified a gene therapy approach to restore Stathmin-2 expression in affected neurons, representing a promising new therapeutic approach for patients with neurodegenerative diseases.

Read abstract of the article:
Mechanism of STMN2 cryptic splice-polyadenylation and its correction for TDP-43 proteinopathies
BY MICHAEL W. BAUGHN, ZE’EV MELAMED, JONE LÓPEZ-ERAUSKIN…Cathleen Lutz, Clotilde Lagier-Tourenne, Don W. Cleveland.
SCIENCE 16 Mar 2023 Vol 379, Issue 6637 pp. 1140-1149 DOI: 10.1126/science.abq5622

Source: Massachusetts General Hospital (MGH)