1-하이드록시피오글리타존염산염

Leriglitazone Hydrochloride is the hydrochloride salt form of leriglitazone, an orally bioavailable, blood-brain-barrier (BBB) penetrable, selective peroxisome proliferator-activated receptor (PPAR) subtype gamma agonist, with potential neuroprotective activity that could be used for certain central nervous system (CNS) diseases, such as adrenomyeloneuropathy, cerebral adrenoleukodystrophy (cALD), Friedreich's ataxia, and certain other CNS diseases. Upon oral administration, leriglitazone selectively targets, binds to and activates PPARgamma, thereby regulating the expression of genes involved in mitochondrial biogenesis. This modulates pathways leading to the restoration of mitochondrial function in which dysfunction is caused by the accumulation of very long-chain fatty acids (VLCFAs), and increases energy production, decreases oxidative stress, decreases nuclear factor kappa B (NF-kB) levels, inhibits neuroinflammation, protects the BBB integrity, prevents demyelination and axonal degeneration, increases neuronal survival, increases myelination and oligodendrocyte survival and improves motor function. Mutations in the ABCD1 gene, which encodes the peroxisomal membrane adrenoleukodystrophy protein, cause a defective function of the ABCD1 transporter leading to an accumulation of VLCFA. VLCFA accumulation contributes to membrane destabilization of the myelin sheath, mitochondrial dysfunction, oxidative stress, neuroinflammation and compromised BBB integrity.