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However, the number of patients suffering from brain diseases is ever increasing and the treatment of brain diseases remains an issue, as drug efficacy is dramatically reduced due to the existence of the unique vascular structure, namely the blood\u2013brain barrier (BBB). Several approaches to enhance drug delivery to the brain have been investigated but many have proven to be unsuccessful due to limited transport or damage induced in the BBB. Alternative approaches to enhance molecular delivery to the brain have been revealed in recent studies through the existence of molecular delivery pathways that regulate the passage of peripheral molecules. In this review, we present recent advancements of the basic research for these delivery pathways as well as examples of promising ventures to overcome the molecular hurdles that will enhance therapeutic interventions in the brain and potentially save the lives of millions of patients.<\/jats:p>","DOI":"10.3390\/cells13100789","type":"journal-article","created":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T03:37:42Z","timestamp":1715053062000},"page":"789","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Hopping the Hurdle: Strategies to Enhance the Molecular Delivery to the Brain through the Blood\u2013Brain Barrier"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0077-0534","authenticated-orcid":false,"given":"Sinnead Anne","family":"Cogill","sequence":"first","affiliation":[{"name":"Dementia Research Group, Korea Brain Research Institute, Daegu 41062, Republic of Korea"},{"name":"Department of Brain & Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Hyeok","family":"Lee","sequence":"additional","affiliation":[{"name":"Dementia Research Group, Korea Brain Research Institute, Daegu 41062, Republic of Korea"},{"name":"Department of Bio and Brain Engineering, Korea Advanced Institute of Science Technology (KAIST), Daejeon 34141, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Tae","family":"Jeon","sequence":"additional","affiliation":[{"name":"Dementia Research Group, Korea Brain Research Institute, Daegu 41062, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Do-Geun","family":"Kim","sequence":"additional","affiliation":[{"name":"Dementia Research Group, Korea Brain Research Institute, Daegu 41062, Republic of Korea"},{"name":"Department of Brain & Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongmin","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea"},{"name":"Department of Radiology, Kyungpook National University Hospital, Daegu 41944, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101333","DOI":"10.1016\/j.arr.2021.101333","article-title":"Emerging pathogenic role of peripheral blood factors following BBB disruption in neurodegenerative disease","volume":"68","author":"Jeon","year":"2021","journal-title":"Ageing Res. 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