{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T04:46:23Z","timestamp":1782535583573,"version":"3.54.5"},"reference-count":65,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CSIR-IICB"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neuroinflammation is a key hallmark of both neurodegenerative and neurospecific autoimmune diseases, including multiple sclerosis (MS), where immune dysregulation contributes to cellular stress, autophagy, and disease progression in Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD), and MS. Emerging evidence suggests a shared mechanism behind MS, AD, and PD, driven by chronic interaction between the peripheral immune system and the central nervous system (CNS). While MS was traditionally viewed as a primary autoimmune condition, recent research indicated that all three disorders involve a breakdown of the blood\u2013brain barrier (BBB). This structural failure enables peripheral immune cells and cytokines to enter the brain, causing sustained neuroinflammation and accelerating disease progression. Here, we propose an end-to-end framework for identification of the diagnostic and therapeutic cell-specific protein markers commonly regulated in mild\u2013moderate AD (MMAD), early-stage PD (ESPD), and MS within peripheral blood mononuclear cells (PBMCs). PBMC markers were first identified based on shared differential protein expression, followed by filtering for BBB permeability. Subsequently, sorted cell markers were mapped to disease-specific neural cell types. Our analysis suggests that PBMC-derived cells, including astrocyte- and monocyte-like populations, share overlapping transcriptional signatures and functional similarity with macrophages and neuroglial cells, indicating potential transcriptional similarity or functional convergence. Furthermore, intra- and inter-cellular pathway analysis suggested both shared and disease-specific signaling mechanisms, with kinase\u2013integrin interactions emerging as key regulatory factors. Selected potential seed markers, primarily kinases and immunoglobulins, were further analyzed through evolutionary sequence\u2013structure space to identify druggable structural features. Next, protein moonlighting possibilities were tested to enhance the temporal functional trajectory of the markers for precise therapeutic impact. Hence, the framework provides a robust strategy to identify immune-based disease-specificcandidate diagnostic andpotential therapeutic targets.<\/jats:p>","DOI":"10.3390\/ijms27125627","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T03:09:17Z","timestamp":1782270557000},"page":"5627","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["IMMUND: A Diagnostic and Therapeutic Pipeline to Uncover the Convergence in Functional Perturbation at Early Stages of Neurodegenerative Diseases and Multiple Sclerosis Based on Protein Markers"],"prefix":"10.3390","volume":"27","author":[{"given":"Ashmita","family":"Dey","sequence":"first","affiliation":[{"name":"Department of Computer Scinece and Engineering, SRM University-AP, Amaravati 522 240, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dwipanjan","family":"Sanyal","sequence":"additional","affiliation":[{"name":"Structural Biology and Bioinformatics, CSIR-Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata 700 032, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1449-8909","authenticated-orcid":false,"given":"Krishnananda","family":"Chattopadhyay","sequence":"additional","affiliation":[{"name":"Structural Biology and Bioinformatics, CSIR-Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata 700 032, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ujjwal","family":"Maulik","sequence":"additional","affiliation":[{"name":"Department of Computer Science and Engineering, Jadavpur University, Kolkata 700 032, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4037-5857","authenticated-orcid":false,"given":"Vladimir N.","family":"Uversky","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and USF Health Byrd Alzheimer\u2019s Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sagnik","family":"Sen","sequence":"additional","affiliation":[{"name":"Department of Computer Science and Engineering, Jadavpur University, Kolkata 700 032, India"},{"name":"Molecular Genetics and Genomics Division, New England Biolabs, Ipswich, MA 01938, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1038\/s41593-018-0242-x","article-title":"Microglia in neurodegeneration","volume":"21","author":"Hickman","year":"2018","journal-title":"Nat. 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