A model for neuroprotective effects of lysosomal cathepsins D and B against mHtt toxicity. A. In Huntington's disease conditions, mHtt cannot be completely degraded and accumulates, leading to neurotoxicity. 3-MA inhibits autophagy activity and exacerbates mHtt-induced neurotoxicity. B. Increasing lysosomal cathepsins D and B reduces mHtt accumulation, and confers neuroprotection. Neuroprotection is dependent on autophagy, since 3-MA reduces cells survival even in the presence of CathD or B.