Pathogenic Impact of Fatty Acid-Binding Proteins in Parkinson’s Disease—Potential Biomarkers and Therapeutic Targets

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.