亨廷頓舞蹈症是一種顯性的遺傳性神經退化性疾病，其致病原因主要是由於亨廷頓(HTT)基因的exon1有CAG三個核甘酸序列的異常擴增，當此帶有CAG異常擴增的亨廷頓(HTT)基因經過轉錄轉譯後會形成帶有延長性多聚谷氨酰胺(polyQ)的突變型亨廷頓蛋白(mHTT)，而錯誤折疊的蛋白無法被順利降解而累積為聚集體(aggregates)，這些聚集體形成神經內包涵體(inclusion bodies, IBs)，影響著神經細胞的功能。亨廷頓相關蛋白40(HAP40)被確定是與亨廷頓蛋白(HTT)交互作用的蛋白，且亨廷頓相關蛋白40(HAP40)的表現量與亨廷頓舞蹈症有密切關聯。實驗室先前的研究中發現亨廷頓相關蛋白40(HAP40)可能與兩種蛋白有交互作用，一個是胸苷酸合成酶(TYMS)，另一個是核醣體蛋白S3(RPS3)。因此我們想利用免疫沉澱法探討這兩個蛋白與亨廷頓相關蛋白40(HAP40)是否存在交互作用。從我們的實驗結果發現胸苷酸合成酶(TYMS)、核醣體蛋白S3(RPS3)皆分別與亨廷頓相關蛋白40(HAP40)有交互作用。最近有研究指出亨廷頓蛋白(HTT)位在粒線體的膜間空間，突變型亨廷頓蛋白(mHTT)位在粒線體的內膜的位置，且突變型亨廷頓蛋白(mHTT)與粒線體內膜蛋白TIM23結合，使得粒線體的轉運機制受阻，進而影響了粒線體的功能。也有研究指出粒線體功能障礙可能是導致亨廷頓舞蹈症的一個原因，突變型亨廷頓蛋白(mHTT)與粒線體結合使得粒線體片段化、氧化壓力上升、ATP能量產生下降，且破壞了鈣離子的平衡。因此我們想探討亨廷頓蛋白(HTT)及亨廷頓相關蛋白40(HAP40)在粒線體中的位置。我們從野生型小鼠的腦組織中分離粒線體，結果發現不管是經過胰蛋白酶(Trypsin)、Triton、洋地黄皂苷(Digitonin)或強鹼處裡，野生型亨廷頓蛋白(HTT)都容易被清除，從我們觀察到的結果得出野生型亨廷頓蛋白(HTT)並沒有進入粒線體內部，更像是在粒線體外側，而亨廷頓相關蛋白40(HAP40)同樣處理後仍然有一部份保留於粒線體中，表明有一部份的亨廷頓相關蛋白40(HAP40)會進到粒線體內部。接著我們想探討在過度表達及降低表達亨廷頓相關蛋白40(HAP40)的情況下，對於粒線體DNA的影響。我們在STHdhQ7/Q7細胞中過度表達及降低表達亨廷頓相關蛋白40，結果發現並不會影響粒線體DNA的拷貝數。在我們的實驗中發現了HTT和HAP40在粒線體中的位置，且表達及降低表達HAP40對於粒線體DNA沒有顯著影響，所以未來我們還可以進一步探討突變型亨廷頓蛋白(mHTT)在粒線體中的分布會不會因為突變而有了位置的改變，同時可以探討在突變型STHdhQ111/Q111細胞相較於野生型STHdhQ7/Q7細胞，粒線體DNA及粒線體功能的變化。

Huntington's disease (HD) is a dominant inherited neurodegenerative disease, which is caused by an abnormal amplification of CAG trinucleotide repeats expansion in exon1 of huntingtin gene. Huntingtin gene with abnormal amplification of CAG will be transcribed and translated to mutant huntingtin protein with polyglutamine. However, misfolded proteins cannot be simply degraded, resulting in the accumulation of protein aggregates, which affect the function of neurons. HAP40 is a 40-kDa protein that interacts with huntingtin, and the expression of HAP40 is closely related to HD. Previous studies in the laboratory found that HAP40 may interact with two proteins, one is TYMS and the other is RPS3. Therefore, we explored whether these two proteins interact with HAP40. Our results show that TYMS and RPS3 interact with HAP40. Recently, it has been indicated that huntingtin locates in the intermembrane space of mitochondria, while mutant huntingtin locates in the inner membrane of mitochondria. The mutant huntingtin interacts with TIM23 in mitochondria, which leads to the damage of mitochondrial transport, and affects the function of mitochondria. As previous study has shown that mitochondrial dysfunction may be one of the causes of HD. The interaction of mutant huntingtin with mitochondria leads to mitochondrial fragmentation, increase of oxidative stress, decrease of ATP production and calcium balance. Thus, we assessed the location of huntingtin and HAP40 in mitochondria. We isolated the mitochondria from the brain tissue of wild-type mice; and found that wild-type huntingtin was easily removed by trypsin, triton, digitonin or alkaline. Our data showed that wild-type huntingtin did not enter the mitochondria, however, a part of HAP40 remained in the mitochondria after the same treatment, indicating that HAP40 enters in the mitochondria and may locate in the inner membrane or the intermembrane space. We also explore the effect of overexpressing or knocking down HAP40 on the mitochondrial DNA, but we found these treatments did not affect the mitochondrial DNA.

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