Norvaline Restores the BBB Integrity in a Mouse Model of Alzheimer's Disease.

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 with AD pathogenesis and presents a potent remedy for angiopathies and neurodegenerative disorders intervention.

• Authors: Baruh Polis, Vyacheslav Gurevich, Michael Assa, Abraham O Samson
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 20 Issue 18 (Sep 18 2019) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 31540372 (Publication Type: Journal Article)

Chemical References

• Amyloid beta-Peptides
• norvaline
• Valine

Topics

• Alzheimer Disease (drug therapy, pathology)
• Amyloid beta-Peptides (analysis)
• Animals
• Astrocytes (drug effects, pathology)
• Blood-Brain Barrier (drug effects, pathology)
• Brain (drug effects, pathology)
• Cerebral Amyloid Angiopathy (drug therapy, pathology)
• Disease Models, Animal
• Male
• Mice, Inbred C57BL
• Mice, Transgenic
• Valine (analogs & derivatives, therapeutic use)