Pharmacological inhibition of FABP7 by MF 6 counteracts cerebellum dysfunction in an experimental multiple system atrophy mouse model

Cheng, An; Jia, Wenbin; Finkelstein, David I.; Stefanova, Nadia; Wang, Haoyang; Sasaki, Takuya; Kawahata, Ichiro; Fukunaga, Kohji

doi:10.1038/s41401-023-01138-y

Cited by 3 publications

(1 citation statement)

References 45 publications

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“…Furthermore, the FABP5 ligand also has the ability to ameliorate FABP3/5induced mitochondrial injury, including lipid peroxidation and BAX-related apoptotic signaling, indicating the potential neuroprotective treatment for ischemic stroke [132,133]. In addition, regarding FABP7, the ligand alleviates FABP7-induced α-synuclein oligomerization and aggregation, thereby rescuing glial and oligodendrocytes from cell death in multiple system atrophy model cells and mice [140,141,143]. These data suggest the promising potential of unique drug developments targeting FABP to regulate dopaminergic signaling and protect neuronal homeostasis.…”

Section: Therapeutic Potential Of Fabp-targeting Drugs For Parkinson'...mentioning

confidence: 99%

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

Kawahata,

Fukunaga

2023

IJMS

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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.

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Section: Therapeutic Potential Of Fabp-targeting Drugs For Parkinson'...mentioning

confidence: 99%

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

Kawahata,

Fukunaga

2023

IJMS

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Potential safety implications of fatty acid-binding protein inhibition

Warren,

Osborn,

Duffy

et al. 2024

Toxicology and Applied Pharmacology

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Fatty acid binding protein type 7 deficiency preserves auditory function in noise-exposed mice

Suzuki,

Hemmi,

Maekawa

et al. 2023

Sci Rep

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Fatty acid-binding protein 7 (FABP7) is vital for uptake and trafficking of fatty acids in the nervous system. To investigate the involvement of FABP7 in noise-induced hearing loss (NIHL) pathogenesis, we used Fabp7 knockout (KO) mice generated via CRISPR/Cas9 in the C57BL/6 background. Initial auditory brainstem response (ABR) measurements were conducted at 9 weeks, followed by noise exposure at 10 weeks. Subsequent ABRs were performed 24 h later, with final measurements at 12 weeks. Inner ears were harvested 24 h after noise exposure for RNA sequencing and metabolic analyses. We found no significant differences in initial ABR measurements, but Fabp7 KO mice showed significantly lower thresholds in the final ABR measurements. Hair cell survival was also enhanced in Fabp7 KO mice. RNA sequencing revealed that genes associated with the electron transport chain were upregulated or less impaired in Fabp7 KO mice. Metabolomic analysis revealed various alterations, including decreased glutamate and aspartate in Fabp7 KO mice. In conclusion, FABP7 deficiency mitigates cochlear damage following noise exposure. This protective effect was supported by the changes in gene expression of the electron transport chain, and in several metabolites, including excitotoxic neurotransmitters. Our study highlights the potential therapeutic significance of targeting FABP7 in NIHL.

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Pharmacological inhibition of FABP7 by MF 6 counteracts cerebellum dysfunction in an experimental multiple system atrophy mouse model

Cited by 3 publications

References 45 publications

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

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

Potential safety implications of fatty acid-binding protein inhibition

Fatty acid binding protein type 7 deficiency preserves auditory function in noise-exposed mice

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