Development of Mitochondria‐targeted Aromatic‐cationic Peptides for Neurodegenerative Diseases
Abstract
Mitochondrial impairment and oxidative damage are intimately involved in the pathogenesis of neurodegenerative diseases. Which is the initiating event is probably irrelevant because each can set into motion a self‐sustaining and amplifying feed‐forward cycle between reactive oxygen species (ROS) generation and mitochondrial impairment. Recent approaches to the development of neuroprotective agents have therefore targeted mitochondria protection and/or reduction of oxidative stress. There are several hurdles in the quest for neuroprotective drugs. The difficulties include penetration of the blood–brain barrier and delivery of drugs to mitochondria. Here we describe a novel class of mitochondria‐targeted peptides that can promote mitochondrial function, reduce mitochondrial ROS generation, inhibit mitochondrial permeability transition, and prevent apoptosis and necrosis. These peptides can readily penetrate the blood–brain barrier and have demonstrated efficacy in animal models of Parkinson's disease and amyotrophic lateral sclerosis.
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Synthetic peptides with antioxidant properties designed to target mitochondria have been shown to penetrate mitochondria targeting the inner membrane by a poorly understood mechanism.
“One involves synthetic peptides with antioxidant properties designed to target mitochondria. These have been shown to penetrate mitochondria targeting the inner membrane by a poorly understood mechanism (304).”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [304]
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Self-citation
- Authors
- Szeto, H. H.
- Affiliations
- Cornell University (US)
- Corresponding author
- Szeto, Hazel H.
- ORCID
- Szeto, Hazel H.
- Venue
- Annals of the New York Academy of Sciences
- Publisher
- Wiley
- Published
- 2008-12
- Volume
- 1147
- Issue
- 1
- Pages
- 112-121
- ISSN
- 0077-8923 (ISSN-L)
- 1749-6632
- OpenAlex
- W2082966118
- Cited by
- 100
- References
- 66
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 3 · 2022: 7 · 2021: 4 · 2020: 5 · 2019: 3 · 2018: 3 · 2017: 4 · 2016: 7 · 2015: 3 · 2014: 8 · 2013: 10 · 2012: 4
- FWCI
- 0.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of the New York Academy of Sciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Drug Abuse (P01DA008924)
- National Institute of Neurological Disorders and Stroke (R21NS048295)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Keywords
- mitochondria-targeted peptide, neurodegenerative diseases, neuroprotection, mitochondrial dysfunction, oxidative stress, reactive oxygen species, mitochondrial permeability transition, blood-brain barrier penetration, Parkinson's disease, amyotrophic lateral sclerosis, apoptosis, necrosis
- MeSH terms
- Adenosine Triphosphate, Animals, Cations, Humans, Mitochondria, Peptides, Reactive Oxygen Species, Oxidative Stress, Neurodegenerative Diseases, Models, Animal
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