A lncRNA survey finds increases in neuroprotective LINC-PINT in Parkinson's disease substantia nigra.

Abstract:

:Recent reports highlight regulatory functions of long noncoding RNAs (lncRNAs) in neurodegeneration and aging, but biomedical implications remain limited. Here, we report an rRNA-depletion-based long RNA-Sequencing Resource of 65 substantia nigra, amygdala, and medial temporal gyrus samples from Parkinson's disease (PD) and matched control brains. Using a lncRNA-focused analysis approach to identify functionally important transcripts, we discovered and prioritized many lncRNAs dysregulated in PD. Those included pronounced elevation of the P53-induced noncoding transcript LINC-PINT in the substantia nigra of PD patients, as well as in additional models of oxidative stress and PD. Intriguingly, we found that LINC-PINT is a primarily neuronal transcript which showed conspicuous increases in maturing primary culture neurons. LINC-PINT also accumulated in several brain regions of Alzheimer's and Huntington's disease patients and decreased with healthy brain aging, suggesting a general role in aging and neurodegeneration for this lncRNA. RNAi-mediated depletion of LINC-PINT exacerbated the death of cultured N2A and SH-SY5Y cells exposed to oxidative stress, highlighting a previously undiscovered neuroprotective role for this tumor-inducible lncRNA in the brains of patients with neurodegenerative disorders.

journal_name

Aging Cell

journal_title

Aging cell

authors

Simchovitz A,Hanan M,Yayon N,Lee S,Bennett ER,Greenberg DS,Kadener S,Soreq H

doi

10.1111/acel.13115

subject

Has Abstract

pub_date

2020-03-01 00:00:00

pages

e13115

issue

3

eissn

1474-9718

issn

1474-9726

journal_volume

19

pub_type

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