Browsing by Subject "Neurodegenerative disorders"
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- PublicationOpen AccessGene therapy for Parkinson's disease: recent achievements and remaining challenges(Murcia : F. Hernández, 2001) Castro, M.G.; David, A.; Hurtado-Lorenzo, A.; Suwelack, D.; Millan, E.; Verakis, T.; Xiong, W.D.; Yuan, X.P.; Lowenstein, P.R.Gene therapy is the use of nucleic acids as drugs. Thus, ways had to be developed to deliver this new generation of drugs to target tissues. Various viral and non-viral vectors have been engineered to carry potentially therapeutic nucleic acids into diseased organs or target cells. The brain offers a particular challenge for gene delivery to its constituent cells: it is encased by the skull, separated from the general circulation by the blood brain barrier, and made up of mostly non-dividing cells. The skull limits direct injection of vectors into the brain, the blood brain barrier inhibits the easy entry of vectors injected into the bloodstream, and post mitotic target cells restrict what type of vector can be used to deliver genes to the brain. We will discuss the main challenges faced by gene delivery to the brain, i.e. immune responses to the delivery vectors and therapeutic transgenes and length of duration of the therapy specifically as applied to Parkinson's disease. We will also discuss therapeutic strategies, which could be implemented to treat Parkinson's disease, and the models in which they have been tested.
- PublicationOpen AccessMelatonin as a mediator of the gut microbiota–host interaction: implications for health and disease(MDPI, 2023-12-23) Rol de Lama, María de los Ángeles; Bonmatí Carrión, María de los Ángeles; FisiologíaIn recent years, the role played by melatonin on the gut microbiota has gained increasingly greater attention. Additionally, the gut microbiota has been proposed as an alternative source of melatonin, suggesting that this antioxidant indoleamine could act as a sort of messenger between the gut microbiota and the host. This review analyses the available scientific literature about possible mechanisms involved in this mediating role, highlighting its antioxidant effects and influence on this interaction. In addition, we also review the available knowledge on the effects of melatonin on gut microbiota composition, as well as its ability to alleviate dysbiosis related to sleep deprivation or chronodisruptive conditions. The melatonin–gut microbiota relationship has also been discussed in terms of its role in the development of different disorders, from inflammatory or metabolic disorders to psychiatric and neurological conditions, also considering oxidative stress and the reactive oxygen species-scavenging properties of melatonin as the main factors mediating this relationship.
- PublicationOpen AccessRegulation and function of sphingosine kinase 2 in diseases(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Song, Dan Dan; Zhou, Jun Hao; Sheng, RuiSphingosine kinase functions to phosphorylate sphingosine to sphingosine 1-phosphate (S1P) to keep balance in the metabolites of sphingolipids. There are two isoforms of sphingosine kinase, sphingosine kinase 1 (SphK1) and sphingosine kinase 2 (SphK2). Although SphK1 and SphK2 share high sequence similarity, SphK2 has distinct distribution, regulation and function. SphK2 is involved in the pathological processes of varieties of diseases including cancer, neurodegenerative disorders, stroke, cardiovascular diseases and inflammation. SphK2 may promote the proliferation of cancer cells and the progression of inflammation. The SphK2/S1P pathway is also involved in the pathogenesis of neurodegenerative disorders and stroke. S1P produced by SphK2 in the nucleus binds to HDACs, which then inhibits histone acetylation and regulates memory. The SphK2 pathway mediates platelet aggregation, thrombosis, cardioprotection and helps to ameliorate hepatic steatosis. This review focuses on the recent advances in research on SphK2 regulation and its potential roles in diseases, highlighting SphK2 may be a novel therapeutic strategy for diseases.