| 摘要 |
Provided herein are methods for treating a subject suffering from a TDP-43 proteinopathy, e.g., sporadic ALS or FTD by administering to the subject a composition comprising a therapeutically effective amount of a JNK inhibitor, a MAPK inhibitor, a proteasome inhibitor, a Topoisomerase I inhibitor, a Topoisomerase II inhibitor, a HSP-90 inhibitor, a 5-HT antagonist, a CDK inhibitor, or a transcription inhibitor. The provided methods can also be used to reduce TDP-43 aggregation in human neural progenitors or neurons in neural progenitors or neurons that exhibit TDP-43 aggregates. In addition, methods are provided to identify agents that modulate (decrease or increase) TDP-43 aggregation in human neural progenitors or neurons that exhibit TDP-43 aggregates. Also provided are human induced pluripotent stem cell (hiPSC) lines generated from sporadic ALS patients, where the hiPSC lines may be differentiated into neural progenitors or neurons (e.g., motor progenitors and motor neurons) that exhibit a TDP-43 aggregate. Further provided are isolated populations of cells containing neural progenitors or neurons derived from the aforementioned hiPSC lines. |
