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Treatment with Cerebrolysin Prolongs Lifespan in a Mouse Model of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy. | LitMetric

AI Article Synopsis

  • CADASIL is a rare genetic neurological disorder linked to NOTCH3 gene mutations, leading to symptoms like migraines, strokes, dementia, and early mortality.
  • Researchers tested the neuropeptide drug Cerebrolysin on NOTCH3 mutant mice, finding it improved spatial memory, health, and lifespan, but didn't change specific white matter issues related to CADASIL.
  • The treatment increased levels of certain beneficial proteins while decreasing others, suggesting that Cerebrolysin could be a potential therapeutic option for CADASIL and conditions related to accelerated aging.

Article Abstract

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare familial neurological disorder caused by mutations in the NOTCH3 gene and characterized by migraine attacks, depressive episodes, lacunar strokes, dementia, and premature death. Since there is no therapy for CADASIL the authors investigate whether the multi-modal neuropeptide drug Cerebrolysin may improve outcome in a murine CADASIL model. Twelve-month-old NOTCH3 mutant mice (n=176) are treated for nine weeks with Cerebrolysin or Vehicle and histopathological and functional outcomes are evaluated within the subsequent ten months. Cerebrolysin treatment improves spatial memory and overall health, reduces epigenetic aging, and prolongs lifespan, however, CADASIL-specific white matter vacuolization is not affected. On the molecular level Cerebrolysin treatment increases expression of Calcitonin Gene-Related Peptide (CGRP) and Silent Information Regulator Two (Sir2)-like protein 6 (SIRT6), decreases expression of Insulin-like Growth Factor 1 (IGF-1), and normalizes the expression of neurovascular laminin. In summary, Cerebrolysin fosters longevity and healthy aging without specifically affecting CADASIL pathology. Hence, Cerebrolysin may serve a therapeutic option for CADASIL and other disorders characterized by accelerated aging.

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Source
http://dx.doi.org/10.1002/adbi.202300439DOI Listing

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