Tet1 deficiency exacerbates oxidative stress in acute kidney injury by regulating superoxide dismutase.

Rationale: Increased methylation of key genes has been observed in kidney diseases, suggesting that the ten-eleven translocation (Tet) methyl-cytosine dioxygenase family as well as 5mC oxidation may play important roles. As a member of the Tet family, the role of Tet1 in acute kidney injury (AKI) remains unclear. Methods: Tet1 knockout mice, with or without tempol treatment, a scavenger of reactive oxygen species (ROS), were challenged with ischemia and reperfusion (I/R) injury or unilateral ureteral obstruction (UUO) injury. RNA-sequencing, Western blotting, qRT-PCR, bisulfite sequencing, chromatin immunoprecipitation, immunohistochemical staining, and dot blot assays were performed. Results: Tet1 expression was rapidly upregulated following I/R or UUO injury. Moreover, Tet1 knockout mice showed increased renal injury and renal cell death, increased ROS accumulation, G2/M cell cycle arrest, inflammation, and fibrosis. Severe renal damage in injured Tet1 knockout mice was alleviated by tempol treatment. Mechanistically, Tet1 reduced the 5mC levels in an enzymatic activity-dependent manner on the promoters of Sod1 and Sod2 to promote their expression, thus lowering injury-induced excessive ROS and reducing I/R or UUO injury. Conclusions: Tet1 plays an important role in the development of AKI by promoting SOD expression through a DNA demethylase-dependent mechanism.

A renal YY1-KIM1-DR5 axis regulates the progression of acute kidney injury.

Acute kidney injury (AKI) exhibits high morbidity and mortality. Kidney injury molecule-1 (KIM1) is dramatically upregulated in renal tubules upon injury, and acts as a biomarker for various renal diseases. However, the exact role and underlying mechanism of KIM1 in the progression of AKI remain elusive. Herein, we report that renal tubular specific knockout of Kim1 attenuates cisplatin- or ischemia/reperfusion-induced AKI in male mice. Mechanistically, transcription factor Yin Yang 1 (YY1), which is downregulated upon AKI, binds to the promoter of KIM1 and represses its expression. Injury-induced KIM1 binds to the ECD domain of death receptor 5 (DR5), which activates DR5 and the following caspase cascade by promoting its multimerization, thus induces renal cell apoptosis and exacerbates AKI. Blocking the KIM1-DR5 interaction with rationally designed peptides exhibit reno-protective effects against AKI. Here, we reveal a YY1-KIM1-DR5 axis in the progression of AKI, which warrants future exploration as therapeutic targets.

Tubular Elabela-APJ axis attenuates ischemia-reperfusion induced acute kidney injury and the following AKI-CKD transition by protecting renal microcirculation.

Rationale: Ischemia-reperfusion injury (I/R) is a common cause of acute kidney injury (AKI). Post-ischemic recovery of renal blood supply plays an important role in attenuating injury. Exogenous application of elabela (ELA) peptides has been demonstrated by us and others to alleviate AKI, partly through its receptor APJ. However, the endogenous role of ELA in renal I/R remains unclear. Methods: Renal tubule specific ELA knockout (ApelaKsp KO) mice challenged with bilateral or unilateral I/R were used to investigate the role of endogenous ELA in renal I/R. RNA-sequencing analysis was performed to unbiasedly investigate altered genes in kidneys of ApelaKsp KO mice. Injured mice were treated with ELA32 peptide, Nω-hydroxy-nor-L-arginine (nor-NOHA), prostaglandin E2 (PGE2), Paricalcitol, ML221 or respective vehicles, individually or in combination. Results: ELA is mostly expressed in renal tubules. Aggravated pathological injury and further reduction of renal microvascular blood flow were observed in ApelaKsp KO mice during AKI and the following transition to chronic kidney disease (AKI-CKD). RNA-seq analysis suggested that two blood flow regulators, arginine metabolizing enzyme arginase 2 (ARG2) and PGE2 metabolizing enzyme carbonyl reductases 1 and 3 (CBR1/3), were altered in injured ApelaKsp KO mice. Notably, combination application of an ARG2 inhibitor nor-NOHA, and Paricalcitol, a clinically used activator for PGE2 synthesis, alleviated injury-induced AKI/AKI-CKD stages and eliminated the worst outcomes observed in ApelaKsp KO mice. Moreover, while the APJ inhibitor ML221 blocked the beneficial effects of ELA32 peptide on AKI, it showed no effect on combination treatment of nor-NOHA and Paricalcitol. Conclusions: An endogenous tubular ELA-APJ axis regulates renal microvascular blood flow that plays a pivotal role in I/R-induced AKI. Furthermore, improving renal blood flow by inhibiting ARG2 and activating PGE2 is an effective treatment for AKI and prevents the subsequent AKI-CKD transition.

Loss of renal tubular G9a benefits acute kidney injury by lowering focal lipid accumulation via CES1.

Surgery-induced renal ischemia and reperfusion (I/R) injury and nephrotoxic drugs like cisplatin can cause acute kidney injury (AKI), for which there is no effective therapy. Lipid accumulation is evident following AKI in renal tubules although the mechanisms and pathological effects are unclear. Here, we report that Ehmt2-encoded histone methyltransferase G9a is upregulated in patients and mouse kidneys after AKI. Renal tubular specific knockout of G9a (Ehmt2Ksp ) or pharmacological inhibition of G9a alleviates lipid accumulation associated with AKI. Mechanistically, G9a suppresses transcription of the lipolytic enzyme Ces1; moreover, G9a and farnesoid X receptor (FXR) competitively bind to the same promoter regions of Ces1. Ces1 is consistently observed to be downregulated in the kidney of AKI patients. Pharmacological inhibition of Ces1 increases lipid accumulation, exacerbates renal I/R-injury and eliminates the beneficial effects on AKI observed in Ehmt2Ksp mice. Furthermore, lipid-lowering atorvastatin and an FXR agonist alleviate AKI by activating Ces1 and reducing renal lipid accumulation. Together, our results reveal a G9a/FXR-Ces1 axis that affects the AKI outcome via regulating renal lipid accumulation.

Probing the interactions between amyloidogenic proteins and bio-membranes.

Protein misfolding diseases (PMDs) in humans are characterized by the deposition of protein aggregates in tissues, including Alzheimer's disease, Parkinson's disease, type 2 diabetes, and amyotrophic lateral sclerosis. Misfolding and aggregation of amyloidogenic proteins play a central role in the onset and progression of PMDs, and these processes are regulated by multiple factors, especially the interaction between proteins and bio-membranes. Bio-membranes induce conformational changes in amyloidogenic proteins and affect their aggregation; on the other hand, the aggregates of amyloidogenic proteins may cause membrane damage or dysfunction leading to cytotoxicity. In this review, we summarize the factors that affect the binding of amyloidogenic proteins and membranes, the effects of bio-membranes on the aggregation of amyloidogenic proteins, mechanisms of membrane disruption by amyloidogenic aggregates, technical approaches for detecting these interactions, and finally therapeutic strategies targeting membrane damage caused by amyloidogenic proteins.

Modelling Parkinson's Disease in C. elegans: Strengths and Limitations.

Parkinson's disease (PD) is a common neurodegenerative disease that affects the motor system and progressively worsens with age. Current treatment options for PD mainly target symptoms, due to our limited understanding of the etiology and pathophysiology of PD. A variety of preclinical models have been developed to study different aspects of the disease. The models have been used to elucidate the pathogenesis and for testing new treatments. These models include cell models, non-mammalian models, rodent models, and non-human primate models. Over the past few decades, Caenorhabditis elegans (C. elegans) has been widely adopted as a model system due to its small size, transparent body, short generation time and life cycle, fully sequenced genome, the tractability of genetic manipulation and suitability for large scale screening for disease modifiers. Here, we review studies using C. elegans as a model for PD and highlight the strengths and limitations of the C. elegans model. Various C. elegans PD models, including neurotoxin-induced models and genetic models, are described in detail. Moreover, met.

Inhibiting protein aggregation with nanomaterials: The underlying mechanisms and impact factors.

Protein aggregation is correlated with the onset and progression of protein misfolding diseases (PMDs). Inhibiting the generation of toxic aggregates of misfolded proteins has been proposed as a therapeutic approach for PMDs. Due to their unique properties, nanomaterials have been extensively investigated for their ability to inhibit protein aggregation and have shown great potential in the diagnosis and treatment of PMDs. However, the precise mechanisms by which nanomaterials interact with amyloidogenic proteins and the factors influencing these interactions remain poorly understood. Consequently, developing a rational design strategy for nanomaterials that target specific proteins in PMDs has been challenging. In this review, we elucidate the effects of nanomaterials on protein aggregation and describe the mechanisms through which nanomaterials interfere with protein aggregation. The major factors impacting protein-nanomaterial interaction such as size, charge, concentration, surface modification and morphology that can be rationally addressed to achieve the desired effects of nanomaterials on protein aggregation are summarized. The prospects and challenges to the clinical application of nanomaterials for the treatment of PMDs are also discussed.

Emerging roles of angiopoietin-like proteins in inflammation: Mechanisms and potential as pharmacological targets.

Angiopoietin-like proteins (ANGPTLs), a family of eight secreted glycoproteins termed ANGTPL1-8, are involved in angiogenesis, lipid metabolism, cancer progression, and inflammation. Their roles in regulating lipid metabolism have been intensively studied, as some ANGPTLs are promising pharmacological targets for hypertriglyceridemia and associated cardiovascular disease. Recently, the emerging roles of ANGPTLs in inflammation have attracted great attention. First, elevated levels of multiple circulating ANGPTLs in inflammatory diseases make them potential disease biomarkers. Second, multiple ANGPTLs regulate acute or chronic inflammation via various mechanisms, including triggering inflammatory signaling through their action as ligands for integrin or forming homo- /hetero-oligomers to regulate signal transduction via extra- or intracellular mechanisms. As dysregulation of the inflammatory response is a critical trigger in many diseases, understanding the roles of ANGPTLs in inflammation will aid in drug/therapy development. Here, we summarize the roles, mechanisms, and potential therapeutic values for ANGPTLs in inflammation and inflammatory diseases.

An automated multiplexed turbidometric and data collection system for measuring growth kinetics of anaerobes dependent on gaseous substrates.

Standard methods of monitoring the growth kinetics of anaerobic microorganisms are generally impractical when there is a protracted or indeterminate period of active growth, and when high numbers of samples or replications are required. As part of our studies of the adaptive evolution of a simple anaerobic syntrophic mutualism, requiring the characterization of many isolates and alternative syntrophic pairings, we developed a multiplexed growth monitoring system using a combination of commercially available electronics and custom designed circuitry and materials. This system automatically monitors up to 64 sealed, and as needed pressurized, culture tubes and reports the growth data in real-time through integration with a customized relational database. The utility of this system was demonstrated by resolving minor differences in growth kinetics associated with the adaptive evolution of a simple microbial community comprised of a sulfate reducing bacterium, Desulfovibrio vulgaris, grown in syntrophic association with Methanococcus maripaludis, a hydrogenotrophic methanogen.

Vitamin C Inhibits the Metabolic Changes Induced by Tet1 Insufficiency Under High Fat Diet Stress.

SCOPE: DNA methylation contributes to obesity, but the role of the DNA demethylase ten-eleven translocation protein 1 (Tet1) in obesity remains unclear. Vitamin C is a cofactor for the Tet family of proteins, but whether vitamin C can be used to treat obesity via Tet1 awaits clarification. METHODS AND RESULTS: Tet1+/+ and Tet1+/- mice are fed a high fat diet (HFD). Higher weight gain and more severe hepatic steatosis, accompanied by reduced 5-hydromethylcytosine (5hmC) levels, are found in the white adipose tissue and liver of Tet1+/- mice. Accumulated lipids are observed in palmitic acid or oleic acid treated primary hepatocytes derived from Tet1+/- mice, which are rescued by Tet1 overexpression or vitamin C treatment. Bisulfite sequencing reveals higher DNA methylation levels on lipolysis related genes in the liver of Tet1+/- mice. Notably, oral intake of vitamin C normalizes DNA methylation levels, promotes lipolysis, and decreases obesity in HFD-fed Tet1+/- mice. CONCLUSIONS: The results reveal a novel function of Tet1 in obesity and provide a new mechanism for the beneficial role of vitamin C in metabolic diseases through enhanced Tet1 activity.

Emerging physiological and pathological roles of MeCP2 in non-neurological systems.

Numerous neurological and non-neurological disorders are associated with dysfunction of epigenetic modulators, and methyl CpG binding protein 2 (MeCP2) is one of such proteins. Initially identified as a transcriptional repressor, MeCP2 specifically binds to methylated DNA, and mutations of MeCP2 have been shown to cause Rett syndrome (RTT), a severe neurological disorder. Recently, accumulating evidence suggests that ubiquitously expressed MeCP2 also plays a central role in non-neurological disorders including cardiac dysfunction, liver injury, respiratory disorders, urological dysfunction, adipose tissue metabolism disorders, movement abnormality and inflammatory responses in a DNA methylation dependent or independent manner. Despite significant progresses in our understanding of MeCP2 over the last few decades, there is still a considerable knowledge gap to translate the in vitro and in vivo experimental findings into therapeutic interventions. In this review, we provide a synopsis of the role of MeCP2 in the pathophysiology of non-neurological disorders, MeCP2-based research directions and therapeutic strategies for non-neurological disorders are also discussed.

Characterization of Anchorless Human PrP With Q227X Stop Mutation Linked to Gerstmann-Sträussler-Scheinker Syndrome In Vivo and In Vitro.

Alteration in cellular prion protein (PrPC) localization on the cell surface through mediation of the glycosylphosphatidylinositol (GPI) anchor has been reported to dramatically affect the formation and infectivity of its pathological isoform (PrPSc). A patient with Gerstmann-Sträussler-Scheinker (GSS) syndrome was previously found to have a nonsense heterozygous PrP-Q227X mutation resulting in an anchorless PrP. However, the allelic origin of this anchorless PrPSc and cellular trafficking of PrPQ227X remain to be determined. Here, we show that PrPSc in the brain of this GSS patient is mainly composed of the mutant but not wild-type PrP (PrPWt), suggesting pathological PrPQ227X is incapable of recruiting PrPWt in vivo. This mutant anchorless protein, however, is able to recruit PrPWt from humanized transgenic mouse brain but not from autopsied human brain homogenates to produce a protease-resistant PrPSc-like form in vitro by protein misfolding cyclic amplification (PMCA). To further investigate the characteristics of this mutation, constructs expressing human PrPQ227X or PrPWt were transfected into neuroblastoma cells (M17). Fractionation of the M17 cells demonstrated that most PrPWt is recovered in the cell lysate fraction, while most of the mutant PrPQ227X is recovered in the medium fraction, consistent with the results obtained by immunofluorescence microscopy. Two-dimensional gel-electrophoresis and Western blotting showed that cellular PrPQ227X spots clustered at molecular weights of 22-25 kDa with an isoelectric point (pI) of 3.5-5.5, whereas protein spots from the medium are at 18-26 kDa with a pI of 7-10. Our findings suggest that the role of GPI anchor in prion propagation between the anchorless mutant PrP and wild-type PrP relies on the cellular distribution of the protein.

Muscular G9a Regulates Muscle-Liver-Fat Axis by Musclin Under Overnutrition in Female Mice.

Cross talk among different tissues and organs is a hotspot in metabolic research. Recent studies have revealed the regulatory roles of a number of myokines in metabolism. Here, we report that female mice lacking muscle-specific histone methylase G9a (Ehmt2 Ckmm knockout [KO] or Ehmt2 HSA KO) are resistant to high-fat diet (HFD)-induced obesity and hepatic steatosis. Furthermore, we identified a significantly upregulated circulating level of musclin, a myokine, in HFD-fed Ehmt2 Ckmm KO or Ehmt2 HSA KO female mice. Similarly, upregulated musclin was observed in mice injected with two structurally different inhibitors for G9a methylase activity: BIX01294 and A366. Moreover, injection of recombinant full-length musclin or its functional core domain inhibited the HFD-induced obesity and hepatic steatosis in wild-type female and male mice. Mechanistically, G9a methylase activity-dependently regulated muscular musclin level by binding to its promoter, also by regulating phosphorylated-FOXO1/FOXO1 levels in vivo and in vitro. Collectively, these data suggest a critical role for G9a in the muscle-liver-fat metabolic axis, at least for female mice. Musclin may serve as a potential therapeutic candidate for obesity and associated diseases.

Loss of histone lysine methyltransferase EZH2 confers resistance to tyrosine kinase inhibitors in non-small cell lung cancer.

Tyrosine kinase inhibitor (TKI) treatment is the first-line therapy for non-small cell lung cancer (NSCLC) caused by activating mutations of epidermal growth factor receptor (EGFR). However, acquired resistance to EGFR-TKI occurs almost inevitably. Aberrant activation of proto-oncogene MET has been known to confer EGFR-TKI resistance; however, the mechanisms involved remains unclear. Recent evidence implicates epigenetic heterogeneity as playing roles in cancer drug resistance, whereas links involving epigenetic heterogeneity and MET in NSCLC remain poorly understood. We found that expression of EZH2, a histone methyltransferase, was negatively correlated with MET activation and EGFR-TKI resistance in NSCLC cells and clinical samples, suggesting the potential for EZH2 to be used as a biomarker for EGFR-TKI sensitivity. Knockdown or inhibition of EZH2 up-regulated MET expression and phosphorylation, and elevated proliferation and EGFR-TKI resistance of cells in vitro. Meanwhile, inhibition of MET or PI3K/AKT enhanced EZH2 levels and restored sensitivity to EGFR-TKI. These findings indicate a "MET-AKT-EZH2" feedback loop regulating EGFR-TKI-resistance. Furthermore, combination therapy of PI3K/AKT inhibition and EGFR-TKI, which interrupts the loop, enhanced tumor-suppressive effects in an EGFR-TKI-resistant xenograft model, indicating a potential approach against drug resistance in NSCLC.

Copper and iron ions accelerate the prion-like propagation of α-synuclein: A vicious cycle in Parkinson's disease.

Protein fibrils drive the onset and progression of many diseases in a prion-like manner, i.e. they transcellular propagate through the extracellular space to health cells to initiate toxic aggregation as seeds. The conversion of native α-synuclein into filamentous aggregates in Lewy bodies is a hallmark of Parkinson's disease (PD). Copper and iron ions accumulate in PD brains, however, whether they influence the prion-like propagation of α-synuclein remain unclear. Here, we reported that copper/iron ions accelerate prion-like propagation of α-synuclein fibrils by promoting cellular internalization of α-synuclein fibrils, intracellular α-synuclein aggregation and the subsequent release of mature fibrils to the extracellular space to induce further propagation. Mechanistically, copper/iron ions enhanced α-synuclein fibrils internalization was mediated by negatively charged membrane heparan sulfate proteoglycans (HSPGs). α-Synuclein fibrils formed in the presence of copper/iron ions were more cytotoxic, causing increased ROS production, cell apoptosis, and shortened the lifespan of a C. elegans PD model overexpressing human α-synuclein. Notably, these deleterious effects were ameliorated by two clinically used chelators, triethylenetetramine and deferiprone. Together, our results suggest a new role for heavy metal ions, e.g. copper and iron, in the pathogenesis of PD through accelerating prion-like propagation of α-synuclein fibrils.

Multigenerational maternal obesity increases the incidence of HCC in offspring via miR-27a-3p.

BACKGROUND & AIMS: Obesity is an independent risk factor for malignancies, including hepatocellular carcinoma (HCC). However, it remains unknown whether maternal obesity affects the incidence of HCC in offspring. Thus, we aimed to investigate this association and its underlying mechanisms. METHODS: Diethylnitrosamine (DEN) was used to induce HCC in a high-fat diet (HFD)-induced multigenerational obesity model. RNA-sequencing was performed to identify the genes and microRNAs (miRNAs) that were altered over generations. The role of the miR-27a-3p-Acsl1/Aldh2 axis in HCC was evaluated in cell lines and HCC-bearing nude mice, and its intergenerational impact was studied in pregnant mice and their offspring. RESULTS: Under HFD stress, maternal obesity caused susceptibility of offspring to DEN-induced HCC, and such susceptibility was cumulative over generations. We identified that Acsl1 and Aldh2, direct targets of miR-27a-3p, were gradually changed over generations. Under hyperlipidemic conditions, downregulation of Acsl1 and Aldh2 increased cell proliferation (in vitro) or tumor growth (in vivo) in synergy. Intratumor injection of an miR-27a-3p agomir exacerbated tumor growth by downregulating Acsl1 and Aldh2; while intratumor injection of an miR-27a-3p antagomir had the opposite effect. Moreover, serum miR-27a-3p levels gradually increased in the HFD-fed maternal lineage over generations. Injecting pregnant mice with an miR-27a-3p agomir not only upregulated hepatic miR-27a-3p and downregulated Acsl1/Aldh2 in offspring (fetus, young and adult stages), but also exacerbated HCC development in DEN-treated offspring. In human HCC, upregulated miR-27a-3p and downregulated Acsl1/Aldh2 were negatively correlated with survival on TCGA analysis; while, hepatic miR-27a-3p was negatively correlated with Acsl1/Aldh2 expression in tumor/non-tumor tissues from fatty/non-fatty livers. CONCLUSIONS: Maternal obesity plays a role in regulating cumulative susceptibility to HCC development in offspring over multiple generations through the miR-27a-3p-Acsl1/Aldh2 axis. LAY SUMMARY: It is not currently known how maternal obesity affects the incidence of liver cancer in offspring. In this study, we identified a microRNA (miR-27a-3p) that was upregulated in obese mothers and could be passed on to their offspring. This microRNA enhanced the risk of liver cancer in offspring by regulating 2 genes (Acsl1 and Aldh2). This mechanism could be a future therapeutic target.

Possible roles of epigenetics in stem cell therapy for Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease with loss of dopaminergic neurons. PD has genetic and epigenetic influences that determine specific changes in the brain. Epigenetic changes result in defective methylation of genes leading to differential gene-expression causing PD. This review provides an overview of stem cell transplantations as potential therapies for PD, with a focus on the epigenetic changes, prior or following transplantation. To date, no reports have addressed epigenetic alterations following stem cell transplantation into the PD brain. Given the potential for affecting the efficacy of stem cell therapy, increased attention needs to be given to the epigenetic processes that occur during stem cell culture and transplantation to maximize the therapeutic potential of stem cells to PD.

Lmo4-resistin signaling contributes to adipose tissue-liver crosstalk upon weight cycling.

Repeated cycles of weight loss and regain, known as weight cycling, is often seen when people try to lose weight. The exact pathophysiological effects and the underlying mechanisms of weight cycling remain largely unclear. Here, we report that weight cycling induced by alternating feeding mice with a low-fat diet or a high-fat diet in a 1-week switch protocol caused further increased epididymal white adipose tissue (eWAT) weight, preadipocyte proliferation, hepatic inflammation, fasting blood glucose level, and glucose intolerance, compared with the continuously HF-fed mice. Combining the secretory protein database with RNA-sequencing and quantitative PCR (qPCR) results in eWAT, the mRNA levels of several adipokines, including Retn (encoding resistin), were found altered by weight cycling. A transcriptional co-factor Lmo4 was found regulated by weight cycling; Lmo4 enhanced preadipocyte proliferation, in vitro adipogenesis, transcription of Retn, and resistin secretion in 3T3-L1 cells. Primary mouse hepatocytes administrated with recombinant mouse resistin (rm-resistin), or exposed to media from Lmo4-overexpressed 3T3-L1 cells, showed increased inflammatory responses and gluconeogenesis. Furthermore, rm-resistin-injected normal chow-fed mice showed upregulated blood glucose level by increasing gluconeogenesis, and upregulated the hepatic inflammatory responses. Together, our results suggest a regulatory role of Lmo4-resistin signaling in weight cycling, indicating a crosstalk between the adipose tissue and liver.

Prion-like mechanisms in neurodegenerative disease: Implications for Huntington's disease therapy.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG repeat expansions in the huntingtin gene resulting in the synthesis of a misfolded form of the huntingtin protein (mHTT) which is toxic. The current treatments for HD are only palliative. Some of the potential therapies for HD include gene therapy (using antisense oligonucleotides and clustered regularly interspaced short palindromic repeats-Cas9 system) and stem-cell-based therapies. Various types of stem cell transplants, such as mesenchymal stem cells, neural stem cells, and reprogrammed stem cells, have the potential to either replace the lost neurons or support the existing neurons by releasing trophic factors. Most of the transplants are xenografts and allografts; however, recent reports on HD patients who received grafts suggest that the mHTT aggregates are transferred from the host neurons to the grafted cells as well as to the surrounding areas of the graft by a "prion-like" mechanism. This observation seems to be true for autotransplantation paradigms, as well. This article reviews the different types of stem cells that have been transplanted into HD patients and their therapeutic efficacy, focusing on the transfer of mHTT from the host cells to the graft. Autotransplants of reprogramed stem cells in HD patients are a promising therapeutic option. However, this needs further attention to ensure a better understanding of the transfer of mHTT aggregates following transplantation of the gene-corrected cells back into the patient.