Norvaline restores the BBB integrity in a mouse model of alzheimer’s disease

Baruh Polis, Vyacheslav Gurevich, Michael Assa, Abraham O. Samson

Research output: Contribution to journalArticlepeer-review

Abstract

Alzheimer’s disease (AD) is a chronic neurodegenerative disorder and the leading cause of dementia. The disease progression is associated with the build-up of amyloid plaques and neurofibrillary tangles in the brain. However, besides the well-defined lesions, the AD-related pathology includes neuroinflammation, compromised energy metabolism, and chronic oxidative stress. Likewise, the blood-brain barrier (BBB) dysfunction is suggested to be a cause and AD consequence. Accordingly, therapeutic targeting of the compromised BBB is a promising disease-modifying approach. We utilized a homozygous triple-transgenic mouse model of AD (3×Tg-AD) to assess the effects of L-norvaline on BBB integrity. We scrutinized the perivascular astrocytes and macrophages by measuring the immunopositive profiles in relation to the presence of β-amyloid and compare the results with those found in wild-type animals. Typically, 3×Tg-AD mice display astroglia cytoskeletal atrophy, associated with the deposition of β-amyloid in the endothelia, and declining nitric oxide synthase (NOS) levels. L-norvaline escalated NOS levels, then reduced rates of BBB permeability, amyloid angiopathy, microgliosis, and astrodegeneration, which suggests AD treatment agent efficacy. Moreover, results undergird the roles of astrodegeneration and microgliosis in AD-associated BBB dysfunction and progressive cognitive impairment. L-norvaline self-evidently interferes withADpathogenesis and presents a potent remedy for angiopathies and neurodegenerative disorders intervention.

Original languageEnglish
Article number4616
JournalInternational Journal of Molecular Sciences
Volume20
Issue number18
DOIs
StatePublished - 2 Sep 2019
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Alzheimer’s disease
  • Angiopathy
  • Arginase
  • Arginine
  • BBB
  • NO
  • NOS
  • Norvaline

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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