{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T06:05:15Z","timestamp":1784613915801,"version":"3.55.0"},"reference-count":255,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"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. Neurosci."],"abstract":"<jats:p>Mitochondria are central regulators of cellular metabolism, redox balance, calcium signaling, and cell survival, making them essential for neuronal function. Because neurons rely heavily on mitochondrial oxidative phosphorylation to meet their high energetic demands, mitochondrial dysfunction has emerged as a key pathogenic driver in major neurodegenerative diseases, including Alzheimer\u2019s disease, Parkinson\u2019s disease, Huntington\u2019s disease, and amyotrophic lateral sclerosis. Defects in mitochondrial bioenergetics, excessive reactive oxygen species production, impaired mitochondrial dynamics, disrupted mitophagy, and dysregulated calcium handling collectively contribute to neuronal damage, synaptic dysfunction, and neuroinflammation. These insights have prompted growing interest in therapeutic strategies that directly target mitochondria to restore organelle homeostasis. Recent advances in chemical biology and nanomedicine have enabled the development of mitochondria-targeted ligands, peptide-based targeting systems, and carrier or nanotechnology-enabled delivery platforms designed to overcome biological barriers and selectively deliver therapeutic cargos to mitochondria within the central nervous system. In this Review, we summarize mitochondrial pathological mechanisms in neurodegenerative diseases and discuss emerging mitochondria-targeted therapeutic strategies, highlighting delivery technologies, therapeutic modalities, and translational challenges. Although most strategies remain at the preclinical or proof-of-principle stage, these advances are beginning to shape a conceptual framework for precision mitochondrial medicine, with the longer-term goal of developing disease-modifying interventions for neurodegenerative disorders.<\/jats:p>","DOI":"10.3389\/fnins.2026.1835506","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T05:36:00Z","timestamp":1784612160000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting mitochondria for the treatment of neurodegenerative diseases"],"prefix":"10.3389","volume":"20","author":[{"given":"Qian","family":"Li","sequence":"first","affiliation":[{"name":"Center for Cancer Prevention, Houston Methodist Cancer Center, Houston Methodist Research Institute","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"You","sequence":"additional","affiliation":[{"name":"Center for Cancer Prevention, Houston Methodist Cancer Center, Houston Methodist Research Institute","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"3657","DOI":"10.1021\/acs.biomac.3c00391","article-title":"Plant mitochondrial-targeted gene delivery by peptide\/DNA micelles quantitatively surface-modified with mitochondrial targeting and membrane-penetrating peptides","volume":"24","author":"Abe","year":"2023","journal-title":"Biomacromolecules"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1834","DOI":"10.3390\/biomedicines9121834","article-title":"Drug delivery challenges in brain disorders across the blood\u2013brain barrier: novel methods and future considerations for improved therapy","volume":"9","author":"Achar","year":"2021","journal-title":"Biomedicine"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.conb.2021.09.005","article-title":"PTEN-induced kinase 1 (PINK1) and parkin: unlocking a mitochondrial quality control pathway linked to Parkinson's disease","volume":"72","author":"Agarwal","year":"2022","journal-title":"Curr. 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