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G. Gray described two different types of synapses in the brain for the first time: symmetric and asymmetric. Later on, symmetric synapses were associated with inhibitory terminals, and asymmetric synapses to excitatory signaling. The balance between these two systems is critical to maintain a correct brain function. Likewise, the modulation of both types of synapses is also important to maintain a healthy equilibrium. Cerebral circuitry responds differently depending on the type of damage and the timeline of the injury. For example, promoting symmetric signaling following ischemic damage is beneficial only during the acute phase; afterwards, it further increases the initial damage. Synapses can be also altered by players not directly related to them; the chronic and long-term neurodegeneration mediated by tau proteins primarily targets asymmetric synapses by decreasing neuronal plasticity and functionality. Dopamine represents the main modulating system within the central nervous system. Indeed, the death of midbrain dopaminergic neurons impairs locomotion, underlying the devastating Parkinson\u2019s disease. Herein, we will review studies on symmetric and asymmetric synapses plasticity after three different stressors: symmetric signaling under acute damage\u2014ischemic stroke; asymmetric signaling under chronic and long-term neurodegeneration\u2014Alzheimer\u2019s disease; symmetric and asymmetric synapses without modulation\u2014Parkinson\u2019s disease.<\/jats:p>","DOI":"10.3390\/sym13122333","type":"journal-article","created":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T02:48:13Z","timestamp":1638845293000},"page":"2333","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Symmetric and Asymmetric Synapses Driving Neurodegenerative Disorders"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7715-1956","authenticated-orcid":false,"given":"Daniel","family":"Romaus-Sanjurjo","sequence":"first","affiliation":[{"name":"NeuroAging Group (NEURAL), Clinical Neurosciences Research Laboratories (LINCs), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1122-0351","authenticated-orcid":false,"given":"Ant\u00eda","family":"Custodia","sequence":"additional","affiliation":[{"name":"NeuroAging Group (NEURAL), Clinical Neurosciences Research Laboratories (LINCs), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1212-9851","authenticated-orcid":false,"given":"Marta","family":"Aramburu-N\u00fa\u00f1ez","sequence":"additional","affiliation":[{"name":"NeuroAging Group (NEURAL), Clinical Neurosciences Research Laboratories (LINCs), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adri\u00e1n","family":"Posado-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"NeuroAging Group (NEURAL), Clinical Neurosciences Research Laboratories (LINCs), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"V\u00e1zquez-V\u00e1zquez","sequence":"additional","affiliation":[{"name":"NeuroAging Group (NEURAL), Clinical Neurosciences Research Laboratories (LINCs), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Camino-Casti\u00f1eiras","sequence":"additional","affiliation":[{"name":"NeuroAging Group (NEURAL), Clinical Neurosciences Research Laboratories (LINCs), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yago","family":"Leira","sequence":"additional","affiliation":[{"name":"NeuroAging Group (NEURAL), Clinical Neurosciences Research Laboratories (LINCs), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Manuel","family":"P\u00edas-Peleteiro","sequence":"additional","affiliation":[{"name":"NeuroAging Group (NEURAL), Clinical Neurosciences Research Laboratories (LINCs), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Manuel","family":"Aldrey","sequence":"additional","affiliation":[{"name":"NeuroAging Group (NEURAL), Clinical Neurosciences Research Laboratories (LINCs), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4359-1704","authenticated-orcid":false,"given":"Alberto","family":"Ouro","sequence":"additional","affiliation":[{"name":"NeuroAging Group (NEURAL), Clinical Neurosciences Research Laboratories (LINCs), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9760-8690","authenticated-orcid":false,"given":"Tom\u00e1s","family":"Sobrino","sequence":"additional","affiliation":[{"name":"NeuroAging Group (NEURAL), Clinical Neurosciences Research Laboratories (LINCs), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,5]]},"reference":[{"key":"ref_1","first-page":"420","article-title":"Axo-somatic and 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