Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 May;9(5):559-566.
doi: 10.1002/sctm.19-0248. Epub 2020 Jan 30.

Prion-like Mechanisms in Neurodegenerative Disease: Implications for Huntington's Disease Therapy

Affiliations
Free PMC article
Review

Prion-like Mechanisms in Neurodegenerative Disease: Implications for Huntington's Disease Therapy

Bhairavi Srinageshwar et al. Stem Cells Transl Med. .
Free PMC article

Abstract

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.

Keywords: Huntington's disease; mHTT aggregates; prion; stem cells; transplantation.

Conflict of interest statement

The authors declared no potential conflicts of interest.

Similar articles

See all similar articles

References

    1. Sugaya K, Vaidya M. Stem cell therapies for neurodegenerative diseases. Adv Exp Med Biol. 2018;1056:61‐84. - PubMed
    1. Haddad MS, Wenceslau CV, Pompeia C, Kerkis I. Cell‐based technologies for Huntington's disease. Dement Neuropsychol. 2016;10:287‐295. - PMC - PubMed
    1. Havel LS, Wang C‐E, Wade B, Huang B, Li S, Li XJ. Preferential accumulation of N‐terminal mutant huntingtin in the nuclei of striatal neurons is regulated by phosphorylation. Hum Mol Genet. 2011;20:1424‐1437. - PMC - PubMed
    1. Thion MS, Humbert S. Cancer: from Wild‐type to mutant Huntingtin. J Huntington Dis. 2018;7:201‐208. - PMC - PubMed
    1. Labbadia J, Morimoto RI. Huntington's disease: underlying molecular mechanisms and emerging concepts. Trends Biochem Sci. 2013;38:378‐385. - PMC - PubMed

LinkOut - more resources

Feedback