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We report that a phenolic\u2010rich extract of avocado\n                    <jats:italic>Persea americana<\/jats:italic>\n                    var. Colinred peel (CRE, 0.01 mg\/ml) restricts environmental neurotoxins paraquat (1 mM)\/maneb (0.05 mM)\u2010induced apoptosis process through blocking reactive oxygen species (ROS) signaling and concomitant inhibition of phosphorylation of LRRK2 in nerve\u2010like cells (NLCs). Indeed, PQ + MB at 6 h exposure significantly increased ROS (57 \u00b1 5%), oxidation of protein DJ\u20101cys106SOH into DJ\u20101Cys106SO3 ([~3.7 f(old)\u2010(i)ncrease]), augmented p\u2010(S935)\u2010LRRK2 kinase (~20\u2010f(old) (i)ncrease), induced nuclei condensation\/fragmentation (28 \u00b1 6%), increased the expression of PUMA (~6.2\u2010fi), and activated CASPASE\u20103 (CASP\u20103, ~4\u2010fi) proteins; but significantly decreased mitochondrial membrane potential (\u0394\u03a8m, ~48 \u00b1 4%), all markers indicative of apoptosis compared to untreated cells. Remarkably, CRE significantly diminished both OS\u2010signals (i.e., DCF+ cells, DJ\u20101Cys106SO3) as well as apoptosis markers (e.g., PUMA, CASP\u20103, loss of \u0394\u03a8m, p\u2010LRRK2 kinase) in NLCs exposed to PQ + MB. Furthermore, CRE dramatically reestablishes the transient intracellular Ca2+ flow (~300%) triggered by dopamine (DA) in neuronal cells exposed to PQ + MB. We conclude that PQ + MB\u2010induced apoptosis in NLCs through OS\u2010mechanism, involving DJ\u20101, PUMA, CASP\u20103, LRRK2 kinase, mitochondria damage, DNA fragmentation, and alteration of DA\u2010receptors. Our findings imply that CRE protects NLCs directly via antioxidant mechanism and indirectly by blocking LRRK2 kinase against PQ + MB stress stimuli. These data suggest that CRE might be a potential natural antioxidant.\n                  <\/jats:p>","DOI":"10.1002\/tox.23433","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T02:27:42Z","timestamp":1639362462000},"page":"660-676","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Phenolic\u2010rich extract of avocado\n                    <i>Persea americana<\/i>\n                    (var. Colinred) peel blunts paraquat\/maneb\u2010induced apoptosis through blocking phosphorylation of\n                    <scp>LRRK2<\/scp>\n                    kinase in human nerve\u2010like cells"],"prefix":"10.1002","volume":"37","author":[{"given":"Diana A.","family":"Quintero\u2010Espinosa","sequence":"first","affiliation":[{"name":"Neuroscience Research Group, Medical Research Institute, Faculty of Medicine University of Antioquia (UdeA)  Medellin Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hector Flavio","family":"Ortega\u2010Arellano","sequence":"additional","affiliation":[{"name":"Neuroscience Research Group, Medical Research Institute, Faculty of Medicine University of Antioquia (UdeA)  Medellin Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0557-0411","authenticated-orcid":false,"given":"Carlos","family":"Velez\u2010Pardo","sequence":"additional","affiliation":[{"name":"Neuroscience Research 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