Impact of Fatty Acid-Binding Proteins in α-Synuclein-Induced Mitochondrial Injury in Synucleinopathy

Synucleinopathies are diverse diseases with motor and cognitive dysfunction due to progressive neuronal loss or demyelination, due to oligodendrocyte loss in the brain. While the etiology of neurodegenerative disorders (NDDs) is likely multifactorial, mitochondrial injury is one of the most vital factors in neuronal loss and oligodendrocyte dysfunction, especially in Parkinson's disease, dementia with Lewy body, multiple system atrophy, and Krabbe disease. In recent years, the abnormal accumulation of highly neurotoxic alpha-synuclein in the mitochondrial membrane, which leads to mitochondrial dysfunction, was well studied. Furthermore, fatty acid-binding proteins (FABPs), which are members of a superfamily and are essential in fatty acid trafficking, were reported to trigger alpha-synuclein oligomerization in neurons and glial cells and to target the mitochondrial outer membrane, thereby causing mitochondrial loss. Here, we provide an updated overview of recent findings on FABP and alpha-synuclein interactions and mitochondrial injury in NDDs.

Automated summary

Synucleinopathies are a group of diverse diseases that can cause motor and cognitive dysfunction due to progressive neuronal loss or demyelination, often found in diseases like Parkinson's and dementia with Lewy bodies. Mitochondrial injury plays a crucial role in neuronal loss and oligodendrocyte dysfunction in these neurodegenerative disorders, with alpha-synuclein accumulation in the mitochondrial membrane being a key factor.