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Despite literature reporting positive effects of betaine supplementation in Alzheimer's, Parkinson's and schizophrenia, the role and function of betaine in the brain are little studied and reviewed. Beneficial effects of betaine in neurodegeneration, excitatory and inhibitory imbalance and against oxidative stress in the central nervous system (CNS) have been collected and analysed to understand the main role of betaine in the brain. There are many \u2018dark\u2019 aspects needed to complete the picture. The understanding of how this osmolyte is transported across neuron and glial cells is also controversial, as the expression levels and functioning of the known protein capable to transport betaine expressed in the brain, betaine\u2010GABA transporter 1 (BGT\u20101), is itself not well clarified. The reported actions of betaine beyond BGT\u20101 related to neuronal degeneration and memory impairment are the focus of this work. With this review, we underline the scarcity of detailed molecular and cellular information about betaine action. Consequently, the requirement of detailed focus on and study of the interaction of this molecule with CNS components to sustain the therapeutic use of betaine.<\/jats:p>","DOI":"10.1111\/bcpt.13839","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T18:14:43Z","timestamp":1675448083000},"page":"485-495","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Betaine\u2014The dark knight of the brain"],"prefix":"10.1111","volume":"133","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5792-0081","authenticated-orcid":false,"given":"Manan","family":"Bhatt","sequence":"first","affiliation":[{"name":"Department of Biotechnology and Life Sciences, Laboratory of Cellular and Molecular Physiology University of Insubria  Varese Italy"},{"name":"School of Experimental and Translational Medicine University of Insubria  Varese 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