TITLE:
Arginase as a Potential Target in the Treatment of Alzheimer’s Disease
AUTHORS:
Baruh Polis, Abraham O. Samson
KEYWORDS:
Alzheimer’s Disease, L-Norvaline, L-Arginine, Arginase
JOURNAL NAME:
Advances in Alzheimer's Disease,
Vol.7 No.4,
November
22,
2018
ABSTRACT: Alzheimer’s disease (AD) is a slowly
progressive, neurodegenerative disorder with an insidious onset that is
characterized by severe decline in memory, thinking and reasoning skills.
Advanced age is a prominent risk factor for AD and other metabolic diseases,
such as type II diabetes and atherosclerosis. Their causal mechanisms are
multifaceted and not fully understood. The precise pathophysiology of AD
remains a mystery despite decades of intensive investigation. Thus far, there
is no truly successful AD therapy. Arginase is the central enzyme of the urea
cycle. Recent studies have identified arginase function in the brain and
associated this enzyme with the development of neurodegenerative diseases.
Upregulation of arginase has been shown to contribute to endothelial
dysfunction, ischemia-reperfusion, atherosclerosis, diabetes, and
neurodegeneration. Other state-of-the-art discoveries of the precise molecular
machinery of neurodegeneration have provided new directions for the rational
development of innovative therapeutic strategies in the treatment of common
neurodegenerative diseases. In this context, the regulation of arginase
activity appears to be a universal approach in interfering with the
pathogenesis of AD and providing relief for it and other metabolic disorders.
Therefore, the enzyme represents a novel therapeutic target. Arginase inhibition
has been shown to reverse amyloid-driven neuronal dysfunction and microgliosis
and prevent the development of other AD symptoms in rodent models of AD.
Consequently, the methodology represents a promising direction for clinical
development.