{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T09:57:15Z","timestamp":1777024635029,"version":"3.51.4"},"reference-count":0,"publisher":"The Nencki Institute of Experimental Biology, Polish Academy of Sciences","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Neurobiol. Exp."],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons. The G2019S mutation in the leucine\u2011rich repeat kinase 2 (LRRK2) gene is the most common genetic cause of familial and sporadic PD. In dopaminergic neurons, increased kinase activity caused by LRRK2\u2011G2019S mutation impairs synaptic vesicle recycling and dopamine storage, increasing cytosolic dopamine, which is prone to oxidation and generates reactive oxygen species. Simultaneously, the mutation alters iron metabolism through Rab misregulation, increasing iron uptake and lysosomal dysfunction, further amplifying oxidative stress and creating a pro\u2011ferroptotic environment. At the same time, dysregulated calcium signaling, driven by the enhanced activity of L\u2011type calcium channels and impaired mitochondrial calcium buffering via the mitochondrial calcium uniporter, enhances mitochondrial dysfunction. This minireview integrates current evidence linking LRRK2\u2011G2019S to these pathological pathways, highlighting this mutation\u2019s role in dopamine, iron, and calcium imbalance. Understanding this molecular interplay may provide novel insights into PD pathogenesis and guide the development of targeted neuroprotective therapies.<\/jats:p>","DOI":"10.55782\/kre63y59","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T09:16:54Z","timestamp":1777022214000},"source":"Crossref","is-referenced-by-count":0,"title":["&lt;i&gt;LRRK2&lt;\/i&gt; mutations: at the crossroads of dopamine, iron, and calcium imbalance in Parkinson\u2019s disease"],"prefix":"10.55782","author":[{"given":"Weronika","family":"Skar\u017cy\u0144ska","sequence":"first","affiliation":[{"name":"International Institute of Molecular and Cell Biology in Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4870-6961","authenticated-orcid":true,"given":"Aleksandra","family":"Moskal","sequence":"additional","affiliation":[{"name":"International Institute of Molecular and Cell Biology in Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacek","family":"Ku\u017anicki","sequence":"additional","affiliation":[{"name":"International Institute of Molecular and Cell Biology in Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"34635","published-online":{"date-parts":[[2026,4,24]]},"container-title":["Acta Neurobiologiae Experimentalis"],"original-title":[],"link":[{"URL":"https:\/\/ane.pl\/index.php\/ane\/article\/download\/2763\/2558","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ane.pl\/index.php\/ane\/article\/download\/2763\/2558","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T09:16:54Z","timestamp":1777022214000},"score":1,"resource":{"primary":{"URL":"https:\/\/ane.pl\/index.php\/ane\/article\/view\/2763"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,24]]},"references-count":0,"URL":"https:\/\/doi.org\/10.55782\/kre63y59","relation":{},"ISSN":["1689-0035","0065-1400"],"issn-type":[{"value":"1689-0035","type":"electronic"},{"value":"0065-1400","type":"print"}],"subject":[],"published":{"date-parts":[[2026,4,24]]}}}