The invention provides compositions and methods for treating neurological disorders, such as amyotrophic lateral sclerosis, frontotemporal degeneration, and Alzheimer’s disease, among others. Using the compositions and methods described herein, a patient having a neurological disorder, such as a neurological disorder associated with TAR-DNA binding protein (TDP)-43 aggregation, may be administered an inhibitor of cytochrome P450 (CYP450) isoform 51A1 (CYP51A1), also referred to herein as lanosterol 14-alpha demethylase, so as to treat an underlying etiology of the disorder and/or to alleviate one or more symptoms of the disease. The inhibitor of CYP51A1 may be a small molecule, anti-CYP51A1 antibody or antigen-binding fragment thereof, or a compound, such as an interfering RNA molecule, that attenuates CYP51A1 expression. Patients that may be treated using the compositions and methods described herein include those that express a mutant TDP-43 isoform containing a mutation associated with TDP-43-promoted aggregation and toxicity.本發明提供用於治療諸如肌肉萎縮性脊髓側索硬化症、額顳性退化、及阿茲海默氏病等等之神經病症之組成物及方法。使用本文所述之該等組成物及方法，患有神經病症諸如與TAR-DNA結合蛋白(TDP)-43聚集相關之神經病症之患者可經投與細胞色素P450(CYP450)同功型51A1(CYP51A1)抑制劑，以便治療該病症之潛在病因及/或減輕該疾病之一或多個症狀，該抑制劑在本文亦稱為羊毛固醇14-α去甲基酶。該CYP51A1抑制劑可為小分子抗CYP51A1抗體或其抗原結合片段或者諸如干擾RNA分子之減弱CYP51A1表現之化合物。可使用本文所述之該等組成物及方法治療之患者包括表現突變型TDP-43同功型之患者，該突變型TDP-43同功型含有與TDP-43促進化聚集及毒性相關之突變。
