Abstract
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 α-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 α-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 α-synuclein interactions and mitochondrial injury in NDDs.
Highlights
Neurodegenerative disorders (NDDs) are characterized by the progressive deterioration of neurons, followed by degeneration of the structure and function of axons, dendrites, and synapses, and leading to neuronal death [1] or dysfunction of myelination [2]
In psychosine-treated oligodendrocytes, we found abnormal accumulation of FABP5 in the mitochondria that formed macropores in the mitochondrial outer membrane (MOM) associated with voltage-dependent anion channels (VDAC)-1 and BCL-2-like protein 4 (BAX) [18]
We reviewed the mitochondrial injury associated with α-synuclein and fatty acid-binding proteins (FABPs) in NDDs, and provided a novel therapeutic target for mitochondrial dysfunction
Summary
Fatty acids with a small number of carbon atoms are water-soluble; long-chain fatty acids with 12 or more carbon atoms are insoluble. The FABP family is a low-molecular-weight intracellular protein, with a molecular weight of 14–15 kDa, and up to 12 types of molecular species were identified in mammals [92] They serve intracellular lipid chaperones and regulate the uptake and transportation of long-chain FAs [93,94], such as eicosanoids and bile acids. FABP7 localizes to the neural stem cells of astrocytes and the hippocampal granule cell layer This suggests high expression levels in the embryonic brain after birth; the expression levels decrease in the mature brain, astrocytes, and OPCs [96,97]. FABP5 is most widely expressed in the epidermis, liver, and adipocytes and is similar to FABP7 It is highly expressed in the nerve and glial cells in embryonic brains but is decreased in mature brains [97,99,100]. Of patients with neurodegenerative disorders, including PD, AD, and other neurological disorders [104,105], suggesting that it might be related to normal brain function and to neurological disease
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