TDP-43 Cryptic RNAs in Perry Syndrome: Differences across Brain Regions and TDP-43 Proteinopathies.

ABSTRACT:

Background

Perry syndrome (PS) is a rare and fatal hereditary autosomal dominant neurodegenerative disorder caused by mutations in dynactin (DCTN1). PS brains accumulate inclusions positive for ubiquitin, transactive-response DNA-binding protein of 43 kDa (TDP-43), and to a lesser extent dynactin.

Objectives

Little is known regarding the contributions of TDP-43, an RNA binding protein that represses cryptic exon inclusion, in PS. Therefore, we sought to identify the degree of TDP-43 dysfunction in two regions of PS brains.

Methods

We evaluated the levels of insoluble pTDP-43 and TDP-43-regulated cryptic RNAs and protein in the caudate nucleus and substantia nigra of 7 PS cases, 12 cases of frontotemporal lobar degeneration (FTLD) with TDP-43 pathology, and 11 cognitiv

SUBMITTER: Pickles SR 

PROVIDER: S-EPMC12006891 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature