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Migraine\u2010related effects, such as cortical spreading depolarization and release of calcitonin gene\u2013related peptide, may initiate adenosine triphosphate (ATP)\u2010mediating pro\u2010nociceptive signaling in the meninges causing headaches. Such signaling may be induced by the interaction of ATP with purinergic receptor P2X 7 (P2X7R) on microglial cells leading to a Ca\n                      <jats:sup>2+<\/jats:sup>\n                      \u2010mediated pH increase in lysosomes and release of autolysosome\u2010like vehicles from microglial cells indicating autophagy impairment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A search in PubMed was conducted with the use of the terms \u201cmigraine,\u201d \u201cautophagy,\u201d \u201cmicroglia,\u201d and \u201cdegradation\u201d in different combinations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Impaired autophagy in microglia may activate secretory autophagy and release of specific proteins, including brain\u2010derived neurotrophic factor (BDNF), which can be also released through the pores induced by P2X7R activation in microglial cells. BDNF may be likewise released from microglial cells upon ATP\u2010 and Ca\n                      <jats:sup>2+<\/jats:sup>\n                      \u2010mediated activation of another purinergic receptor, P2X4R. BDNF released from microglia might induce autophagy in neurons to clear cellular debris produced by oxidative stress, which is induced in the brain as the response to migraine\u2010related energy deficit. Therefore, migraine\u2010related signaling may impair degradative autophagy, stimulate secretory autophagy in microglia, and degradative autophagy in neurons. These effects are mediated by purinergic receptors P2X4R and P2X7R, BDNF, ATP, and Ca\n                      <jats:sup>2+<\/jats:sup>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Different effects of migraine\u2010related events on degradative autophagy in microglia and neurons may prevent prolonged changes in the brain related to headache attacks.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.14625","type":"journal-article","created":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T04:49:01Z","timestamp":1693198141000},"page":"1154-1166","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Autophagy may protect the brain against prolonged consequences of headache attacks: A narrative\/hypothesis 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