Prospects for Diminishing the Impact of Nonamyloid Small-Vessel Diseases of the Brain

Small-vessel diseases (SVDs) of the brain are involved in about one-fourth of ischemic strokes and a vast majority of intracerebral hemorrhages and are responsible for nearly half of dementia cases in the elderly. SVDs are a heavy burden for society, a burden that is expected to increase further in the absence of significant therapeutic advances, given the aging population. Here, we provide a critical appraisal of currently available therapeutic approaches for nonamyloid sporadic SVDs that are largely based on targeting modifiable risk factors. We review what is known about the pathogenic mechanisms of vascular risk factor-related SVDs and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most frequent hereditary SVD, and elaborate on two mechanism-based therapeutic approaches worth exploring in sporadic SVD and CADASIL. We conclude by discussing opportunities and challenges that need to be tackled if efforts to achieve significant therapeutic advances for these diseases are to be successful.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:60

Enthalten in:

Annual review of pharmacology and toxicology - 60(2020) vom: 06. Jan., Seite 437-456

Sprache:

Englisch

Beteiligte Personen:

Joutel, Anne [VerfasserIn]

Links:

Volltext

Themen:

CADASIL
Endothelial dysfunction
Hypertension
Journal Article
NOTCH3
Research Support, Non-U.S. Gov't
Review
Small-vessel diseases

Anmerkungen:

Date Completed 11.11.2020

Date Revised 11.11.2020

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1146/annurev-pharmtox-010818-021712

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM300350295