Mitochondrial Dysfunction in Diabetic Neuropathy: An Evidence Map of Molecular Mechanisms, Translational Biomarkers, and Emerging Implications for Oral Neuropathy-A Scoping Review.
6 affiliations
- 1Department of Oral Medicine, Faculty of Dentistry, Universitas Hang Tuah, Surabaya 60111, Indonesia.
- 2Department of Physiology, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Chennai 600077, Tamil Nadu, India.
- 3Research Institute of Oral Science, School of Dentistry at Matsudo, Nihon University, Chiba 271-8587, Japan.
- 4Nanozyme Laboratory in Zhongyuan, Aging Decoding and Regeneration Institute, School of Basic Medical Sciences, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, Zhengzhou University, Zhengzhou 450001, China.
- 5Department of Human Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China.
- 6Department of Oral Biology, Faculty of Dentistry, Universitas Hang Tuah, Surabaya 60111, Indonesia.
Abstract
Diabetic peripheral neuropathy (DPN) is a common and disabling complication of diabetes, but treatment still focuses largely on symptom control rather than modification of the underlying nerve injury. Mitochondrial dysfunction is increasingly implicated in the response of peripheral nerves to chronic hyperglycemia, although the literature is spread across different mitochondrial pathways, experimental models, biomarkers, and clinical settings. We therefore conducted a scoping review, following the Joanna Briggs Institute framework, to map this evidence and examine how far it has extended to oral and craniofacial neuropathic manifestations. PubMed, Scopus, and SpringerLink were searched using a predefined Population-Concept-Context strategy, and two reviewers independently screened records in Rayyan. Of 40,863 records identified, 853 studies met the eligibility criteria; 462 (54.2%) were published between 2021 and 2026. Most studies were preclinical. In the hierarchical evidence map, oxidative stress/redox imbalance was the largest evidence-mapping category (n = 591; 69.3%), followed by Schwann-cell degeneration (n = 147; 17.2%) and bioenergetic dysfunction (n = 77; 9.0%), whereas mitophagy (n = 14; 1.6%) and mitochondrial dynamics (n = 14; 1.6%) were much less frequently represented. Craniofacial neuropathy (n = 6; 0.7%) and oral neuropathy (n = 4; 0.5%) represented only a small proportion of the evidence map. Across these domains, recurrent pathways included Nrf2/Keap1 antioxidant defense, NF-κB-associated neuroinflammation, mitochondria-dependent apoptosis, and AMPK-SIRT-PGC-1α signaling. Clinical translation was limited, although mitochondrial DNA copy number, SOD3, and 8-hydroxy-2'-deoxyguanosine were reported as candidate biomarkers. Overall, the expanded evidence base confirms substantial growth in mitochondrial research in diabetic neuropathy but remains predominantly preclinical, with a particularly pronounced translational gap in oral and craniofacial neuropathy.
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BibTeX
@article{rahman2026mitochondrial,
title = {{Mitochondrial Dysfunction in Diabetic Neuropathy: An Evidence Map of Molecular Mechanisms, Translational Biomarkers, and Emerging Implications for Oral Neuropathy-A Scoping Review.}},
author = {Kurnia Hayati Rahman and Ujjal K Bhawal and Jian Wang and Junmin Wang and Kristanti Parisihni},
journal = {International journal of molecular sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198647},
url = {https://europepmc.org/article/MED/42883893},
note = {CC BY},
}
RIS
TY - JOUR
TI - Mitochondrial Dysfunction in Diabetic Neuropathy: An Evidence Map of Molecular Mechanisms, Translational Biomarkers, and Emerging Implications for Oral Neuropathy-A Scoping Review.
AU - Kurnia Hayati Rahman
AU - Ujjal K Bhawal
AU - Jian Wang
AU - Junmin Wang
AU - Kristanti Parisihni
PY - 2026
DA - 2026/09/27
JO - International journal of molecular sciences
DO - 10.3390/ijms27198647
UR - https://europepmc.org/article/MED/42883893
AB - Diabetic peripheral neuropathy (DPN) is a common and disabling complication of diabetes, but treatment still focuses largely on symptom control rather than modification of the underlying nerve injury. Mitochondrial dysfunction is increasingly implicated in the response of peripheral nerves to chronic hyperglycemia, although the literature is spread across different mitochondrial pathways, experimental models, biomarkers, and clinical settings. We therefore conducted a scoping review, following the Joanna Briggs Institute framework, to map this evidence and examine how far it has extended to oral and craniofacial neuropathic manifestations. PubMed, Scopus, and SpringerLink were searched using a predefined Population-Concept-Context strategy, and two reviewers independently screened records in Rayyan. Of 40,863 records identified, 853 studies met the eligibility criteria; 462 (54.2%) were published between 2021 and 2026. Most studies were preclinical. In the hierarchical evidence map, oxidative stress/redox imbalance was the largest evidence-mapping category (n = 591; 69.3%), followed by Schwann-cell degeneration (n = 147; 17.2%) and bioenergetic dysfunction (n = 77; 9.0%), whereas mitophagy (n = 14; 1.6%) and mitochondrial dynamics (n = 14; 1.6%) were much less frequently represented. Craniofacial neuropathy (n = 6; 0.7%) and oral neuropathy (n = 4; 0.5%) represented only a small proportion of the evidence map. Across these domains, recurrent pathways included Nrf2/Keap1 antioxidant defense, NF-κB-associated neuroinflammation, mitochondria-dependent apoptosis, and AMPK-SIRT-PGC-1α signaling. Clinical translation was limited, although mitochondrial DNA copy number, SOD3, and 8-hydroxy-2'-deoxyguanosine were reported as candidate biomarkers. Overall, the expanded evidence base confirms substantial growth in mitochondrial research in diabetic neuropathy but remains predominantly preclinical, with a particularly pronounced translational gap in oral and craniofacial neuropathy.
SN - 1422-0067
ER -