Afegostat (D-Isofagomine)

Afegostat (D-Isofagomine) 是一种药理学伴侣，它以高亲和力特异性和可逆地结合内质网 (ER) 中的 acid-β-葡萄糖苷酶 (GCase)。

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Background

Afegostat is a pharmacological chaperone, which specifically and reversibly binds acid-β-glucosidase (GCase) in the endoplasmic reticulum (ER) with high affinity[1].

Afegostat (AT2101) increases GCase activity in brain, liver, and spleen. Afegostat (100 mg/kg) administrates orally for 4 months to Thy1-aSyn mice improved motor and nonmotor function, abolishes microglial inflammatory response in the substantia nigra, reduces α-synuclein immunoreactivity in nigral dopaminergic neurons, and reduces the number of small α-synuclein aggregates, while increasing the number of large α-synuclein aggregates[1].

[1]. Richter F, et al. A GCase chaperone improves motor function in a mouse model of synucleinopathy. Neurotherapeutics. 2014 Oct;11(4):840-56.