Editing Huntington's disease (section)

===Huntingtin function===
{{See also|Huntingtin#Function}}
Htt is [[gene expression|expressed]] in all cells, with the highest concentrations found in the brain and [[testes]], and moderate amounts in the [[liver]], [[heart]], and [[lung]]s. Although its full range of functions is not yet understood, Htt interacts with proteins involved in [[Transcription (biology)|transcription]], [[cell signaling]], and [[Vesicle (biology)#Transport vesicles|intracellular transport]].<ref name="Liu"/> Studies in [[Genetically modified organism|genetically modified animals]] have shown that wild-type Htt is essential for embryonic development, as complete absence of the gene results in embryonic death.<ref name="Httfunction">{{cite journal | vauthors = Cattaneo E, Zuccato C, Tartari M | title = Normal huntingtin function: an alternative approach to Huntington's disease | journal = Nature Reviews. Neuroscience | volume = 6 | issue = 12 | pages = 919–930 | date = December 2005 | pmid = 16288298 | doi = 10.1038/nrn1806 | s2cid = 10119487 }}</ref> Htt also plays a protective role in mature neurons: it regulates the production of [[brain-derived neurotrophic factor]], supports [[Synaptic vesicle|synaptic vesicular transport]] and [[synaptic transmission]], controls neuronal gene transcription, and prevents programmed cell death by inhibiting [[Apoptosis|apoptotic]] enzymes such as [[Caspase|caspases]].<ref name="Httfunction"/> In contrast to these protective roles, the mutant form of the protein (mHtt) interferes with the [[Proteasome#Protein_degradation_process|ubiquitin-proteasome system]], which promotes caspase activation, contributing to neurodegeneration. Increasing the expression of Htt can promote [[Neuron|brain cell]] survival and ameliorate the effects of mHtt, whereas reducing it can exacerbate those effects.<ref name="Httfunction"/>  Accordingly, the disease is thought not to be caused by [[haploinsufficiency|inadequate expression]] of Htt, but by a [[Gain-of-function|toxic gain-of-function]] of mHtt in the body.<ref name="lancet07" /> The mutant protein is expressed throughout the body and associated with abnormalities in peripheral tissues outside of the brain, which can include [[muscle atrophy]], [[cardiac failure]], [[impaired glucose tolerance]], [[weight loss]], [[osteoporosis]], and [[testicular atrophy]].<ref>{{cite journal | vauthors = van der Burg JM, Björkqvist M, Brundin P | title = Beyond the brain: widespread pathology in Huntington's disease | journal = The Lancet. Neurology | volume = 8 | issue = 8 | pages = 765–774 | date = August 2009 | pmid = 19608102 | doi = 10.1016/S1474-4422(09)70178-4 | s2cid = 14419437 }}</ref>