{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T06:15:40Z","timestamp":1788156940265,"version":"build-2803163510"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>\n                    Parkinson\u2019s disease (PD) is characterized by progressive \u03b1-synuclein aggregation, yet the molecular mechanisms underlying this process remain incompletely understood. Transcriptomic analyses may provide important insights into the RNA-mediated regulation of PD pathogenesis, but studies of affected brain tissue are limited by the inaccessibility of living brain tissue and post-mortem RNA degradation. The submandibular gland (SMG), which exhibits \u03b1-synuclein pathology comparable to that of the substantia nigra, represents a clinically accessible peripheral tissue for investigating disease-associated transcriptomic alterations. However, ultrasound-guided core needle biopsy yields only a limited amount of tissue, making comprehensive RNA sequencing technically challenging. Here, we present and validate a workflow for paired total RNA and small RNA sequencing from low-input SMG biopsy specimens obtained from patients with\n                    <jats:italic>de novo<\/jats:italic>\n                    PD and age-matched, neurologically unaffected surgical controls. Ultrasound-guided core needle biopsy yielded specimens measuring approximately 1.2 \u00d7 7\u201310 mm. To enable direct tissue-to-blood comparisons, fasting peripheral blood samples were collected from the same participants on the morning of biopsy. Following immediate tissue stabilization, RNA extraction, library preparation, and next-generation sequencing, workflow performance was evaluated by assessing RNA integrity, library quality, sequencing metrics, mapping performance, and reproducibility. Despite the limited tissue input, the protocol consistently generated high-quality RNA suitable for both total RNA sequencing and small RNA sequencing. The validated workflow produced robust sequencing libraries with high reproducibility and enabled comprehensive profiling of protein-coding transcripts together with multiple classes of small non-coding RNAs, including miRNAs, piRNAs, snoRNAs, snRNAs, and tRNA-derived RNAs. This validated workflow provides a practical and reproducible approach for comprehensive transcriptomic profiling of minimally invasive SMG biopsy specimens and matched fasting peripheral blood, and may facilitate future studies of disease mechanisms, biomarker discovery, and translational applications in Parkinson\u2019s disease.\n                  <\/jats:p>","DOI":"10.3389\/fnagi.2026.1931183","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T05:40:10Z","timestamp":1788154810000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A validated workflow for paired total and small RNA sequencing from low-input submandibular gland biopsy specimens in de novo Parkinson\u2019s disease patients"],"prefix":"10.3389","volume":"18","author":[{"given":"Ko-Eun","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Anatomy, Korea University College of Medicine","place":["Seoul, Republic of Korea"]},{"name":"Department of Neurology, College of Medicine, The Catholic University of Korea","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joong-Seok","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology, College of Medicine, The Catholic University of Korea","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"4183","DOI":"10.1038\/s41467-020-17876-0","article-title":"A single-cell atlas of the human substantia nigra reveals cell-specific pathways associated with neurological disorders.","volume":"11","author":"Agarwal","year":"2020","journal-title":"Nat. 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