3.3.3. Rapamycin

mTOR is a protein kinase that phosphorylates many proteins and plays a key role in various cellular functions (like autophagy and transcription). mTOR interacts with mHTT and localizes to these polyglutamine aggregates, and thus sequestration of mTOR reduces the activity of mTOR, resulting in a decrease in autophagy and a decrease in the clearance of mHTT. mTOR phosphorylates S6K1 (a key regulator of cell volume), therefore mHTT-related impairment of mTOR may account for the brain atrophy in HD. Rapamycin (which inhibits mTOR and consequently induces autophagy) decreased mHTT aggregates and improved neuronal survival in the drosophila HD model. Rapamycin also improved motor performance and decreased striatal neuropathology in mouse models of HD [54–56].


**Table 1.** Recent status of Huntington's disease (HD) drug therapy.


#### **Table 1.** *Cont.*

**Figure 2.** Recent advancement in the therapeutics for Huntington's disease. TBZ (Tetrabenazine); EPA (eicosapentaenoic acid); MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine); SAHA (suberoylanilide hydroxamic acid); HDACi4b (histone deacetylase inhibitors); RNAi (RNA interference); ASO (antisense oligonucleotide); ZFP (zinc finger protein); CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats); miRNA (micro RNA); siRNA (small interfering RNA).

#### *3.4. Targeting Mitochondrial Dysfunction*
