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Chronic Pb exposure remains a major public health concern, particularly in developing countries, and is associated with cognitive impairment, memory deficits, and peripheral and central nervous system toxicity. Pb readily crosses the blood\u2013brain barrier by competing with iron for transport via divalent metal transporter 1 and mimicking calcium to enter through Ca\u2010permeable ion channels, thereby disrupting Fe homeostasis and blood\u2013brain barrier integrity. Pb accumulation promotes excessive generation of reactive oxygen species, mitochondrial dysfunction, lipid peroxidation, and neuroinflammatory responses in the brain. These events alter apoptotic signaling pathways, impair Ca\u2010dependent neuronal communication, and disrupt cholinergic neurotransmission, leading to synaptic dysfunction and neuronal loss in the hippocampus. Proteomic studies have provided insights into the molecular mechanisms underlying Pb\u2010induced neurotoxicity by identifying various Pb\u2010interacting proteins involved in metal transport, oxidative stress regulation, apoptosis, synaptic plasticity, and neurotransmitter signaling. In the absence of effective pharmaceutical treatments for Pb poisoning, these proteomic insights highlight potential diagnostic biomarkers and therapeutic targets that play a central role in antioxidant defense and inflammation control. Emerging enzymatic biosensors also offer promising tools for the rapid and sensitive detection of Pb exposure. Collectively, this review integrates mechanistic, proteomic, and translational perspectives to understand Pb\u2010induced neurotoxicity and support the development of improved diagnostic and mitigation strategies for Pb exposure.<\/jats:p>","DOI":"10.1002\/jat.70123","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:44:49Z","timestamp":1771807489000},"page":"1713-1722","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Proteomic Mapping of Hippocampal Pathways Involved in Lead (Pb)\u2013Induced Neurotoxicity"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0598-5800","authenticated-orcid":false,"given":"Kartikey","family":"Matte","sequence":"first","affiliation":[{"name":"Department of Biochemistry ICMR\u2010Regional Occupational Health Centre (Southern)  Bengaluru India"},{"name":"School of Applied Sciences REVA University  Bengaluru India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7742-7809","authenticated-orcid":false,"given":"Shubhangi","family":"Pingle","sequence":"additional","affiliation":[{"name":"Department of Biochemistry ICMR\u2010Regional Occupational Health Centre (Southern)  Bengaluru India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manjula\u00a0Kannasandra","family":"Ramaiah","sequence":"additional","affiliation":[{"name":"School of Applied Sciences REVA University  Bengaluru India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajani","family":"Tumane","sequence":"additional","affiliation":[{"name":"Department of Biochemistry ICMR\u2010Regional Occupational Health Centre (Southern)  Bengaluru India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6489-7899","authenticated-orcid":false,"given":"Prasad","family":"Sherekar","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Priyadarshini College of Engineering  Nagpur India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,22]]},"reference":[{"key":"e_1_2_13_2_1","unstructured":"Abadin H. 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