{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T12:28:50Z","timestamp":1791808130404,"version":"4.3.4"},"reference-count":177,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2020,8,27]],"date-time":"2020-08-27T00:00:00Z","timestamp":1598486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technology and Innovation, Colombia","award":["Grant ID 120380763212 \u2013 PPTA # 8352"],"award-info":[{"award-number":["Grant ID 120380763212 \u2013 PPTA # 8352"]}]},{"name":"Ministry of Science, Technology and Innovation, Colombia","award":["Young researcher fellowship (Contract 829-2018 \u2013 PPTA #8728 and #8729)"],"award-info":[{"award-number":["Young researcher fellowship (Contract 829-2018 \u2013 PPTA #8728 and #8729)"]}]},{"DOI":"10.13039\/501100009543","name":"Pontificia Universidad Javeriana","doi-asserted-by":"publisher","award":["PPTA # 8275"],"award-info":[{"award-number":["PPTA # 8275"]}],"id":[{"id":"10.13039\/501100009543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>GM2 gangliosidoses are a group of pathologies characterized by GM2 ganglioside accumulation into the lysosome due to mutations on the genes encoding for the \u03b2-hexosaminidases subunits or the GM2 activator protein. Three GM2 gangliosidoses have been described: Tay\u2013Sachs disease, Sandhoff disease, and the AB variant. Central nervous system dysfunction is the main characteristic of GM2 gangliosidoses patients that include neurodevelopment alterations, neuroinflammation, and neuronal apoptosis. Currently, there is not approved therapy for GM2 gangliosidoses, but different therapeutic strategies have been studied including hematopoietic stem cell transplantation, enzyme replacement therapy, substrate reduction therapy, pharmacological chaperones, and gene therapy. The blood\u2013brain barrier represents a challenge for the development of therapeutic agents for these disorders. In this sense, alternative routes of administration (e.g., intrathecal or intracerebroventricular) have been evaluated, as well as the design of fusion peptides that allow the protein transport from the brain capillaries to the central nervous system. In this review, we outline the current knowledge about clinical and physiopathological findings of GM2 gangliosidoses, as well as the ongoing proposals to overcome some limitations of the traditional alternatives by using novel strategies such as molecular Trojan horses or advanced tools of genome editing.<\/jats:p>","DOI":"10.3390\/ijms21176213","type":"journal-article","created":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T09:17:08Z","timestamp":1598606228000},"page":"6213","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":107,"title":["GM2 Gangliosidoses: Clinical Features, Pathophysiological Aspects, and Current Therapies"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5956-1986","authenticated-orcid":false,"given":"Andr\u00e9s Felipe","family":"Leal","sequence":"first","affiliation":[{"name":"Institute for the Study of Inborn Errors of Metabolism, Faculty of Science, Pontificia Universidad Javeriana, Bogot\u00e1 110231, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliana","family":"Benincore-Fl\u00f3rez","sequence":"additional","affiliation":[{"name":"Institute for the Study of Inborn Errors of Metabolism, Faculty of Science, Pontificia Universidad Javeriana, Bogot\u00e1 110231, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Solano-Galarza","sequence":"additional","affiliation":[{"name":"Institute for the Study of Inborn Errors of Metabolism, Faculty of Science, Pontificia Universidad Javeriana, Bogot\u00e1 110231, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8102-6821","authenticated-orcid":false,"given":"Rafael Guillermo","family":"Garz\u00f3n Jaramillo","sequence":"additional","affiliation":[{"name":"Institute for the Study of Inborn Errors of Metabolism, Faculty of Science, Pontificia Universidad Javeriana, Bogot\u00e1 110231, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga Yaneth","family":"Echeverri-Pe\u00f1a","sequence":"additional","affiliation":[{"name":"Institute for the Study of Inborn Errors of Metabolism, Faculty of Science, Pontificia Universidad Javeriana, Bogot\u00e1 110231, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego A.","family":"Suarez","sequence":"additional","affiliation":[{"name":"Institute for the Study of Inborn Errors of Metabolism, Faculty of Science, Pontificia Universidad Javeriana, Bogot\u00e1 110231, Colombia"},{"name":"Faculty of Medicine, Universidad Nacional de Colombia, Bogot\u00e1 110231, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6484-1173","authenticated-orcid":false,"given":"Carlos Javier","family":"Alm\u00e9ciga-D\u00edaz","sequence":"additional","affiliation":[{"name":"Institute for the Study of Inborn Errors of Metabolism, Faculty of Science, Pontificia Universidad Javeriana, Bogot\u00e1 110231, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9670-6435","authenticated-orcid":false,"given":"Angela Johana","family":"Espejo-Mojica","sequence":"additional","affiliation":[{"name":"Institute for the Study of Inborn Errors of Metabolism, Faculty of Science, Pontificia Universidad Javeriana, Bogot\u00e1 110231, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10195","DOI":"10.1523\/JNEUROSCI.0822-13.2013","article-title":"Gangliosides and Gangliosidoses: Principles of Molecular and Metabolic Pathogenesis","volume":"33","author":"Sandhoff","year":"2013","journal-title":"J. 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