Affiliation:
1. Department of CNS Drug Innovation, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan
2. BRI Pharma Inc., Sendai 982-0804, Japan
Abstract
Parkinson’s disease is a neurodegenerative condition characterized by motor dysfunction resulting from the degeneration of dopamine-producing neurons in the midbrain. This dopamine deficiency gives rise to a spectrum of movement-related symptoms, including tremors, rigidity, and bradykinesia. While the precise etiology of Parkinson’s disease remains elusive, genetic mutations, protein aggregation, inflammatory processes, and oxidative stress are believed to contribute to its development. In this context, fatty acid-binding proteins (FABPs) in the central nervous system, FABP3, FABP5, and FABP7, impact α-synuclein aggregation, neurotoxicity, and neuroinflammation. These FABPs accumulate in mitochondria during neurodegeneration, disrupting their membrane potential and homeostasis. In particular, FABP3, abundant in nigrostriatal dopaminergic neurons, is responsible for α-synuclein propagation into neurons and intracellular accumulation, affecting the loss of mesencephalic tyrosine hydroxylase protein, a rate-limiting enzyme of dopamine biosynthesis. This review summarizes the characteristics of FABP family proteins and delves into the pathogenic significance of FABPs in the pathogenesis of Parkinson’s disease. Furthermore, it examines potential novel therapeutic targets and early diagnostic biomarkers for Parkinson’s disease and related neurodegenerative disorders.
Funder
Japan Agency for Medical Research and Development
Japan AMED
Japan Society for the Promotion of Science (JSPS) KAKENHI
Takeda Science Foundation
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis