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Pantethine and Neurodegeneration: A Coenzyme A-Centered Framework Linking Metabolism, Neuroinflammation, and Mitochondrial Dysfunction
Garcia Simili OA, Magno de Carvalho G, Santana Dias Simões R, Rucco Penteado Detregiachi C, de Souza Bastos Mazuqueli Pereira E, Cavallari Strozze Catharin VM, da Silva GA, Miola VB et al.. Preprints.org, 2026-10-23
Topic: Gut, metabolism and diet
Neurodegenerative diseases are a growing global health burden associated with aging and characterized by progressive neuronal dysfunction, metabolic failure, mitochondrial impairment, oxidative stress, and chronic neuroinflammation. Among the metabolic pathways implicated in these disorders, coenzyme A (CoA)-linked biology has emerged as a potentially important but still underexplored contributor to neuronal resilience and vulnerability. Pantethine, a disulfide derivative of pantetheine and a CoA-related metabolic precursor, has attracted attention because of its reported effects on cellular metabolism, redox balance, and inflammatory signaling. However, its relevance across neurodegenerative diseases remains unevenly defined, with direct support strongest in pantothenate kinase-associated neurodegeneration (PKAN) and more limited evidence in common disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). This narrative review critically examines the mechanistic and translational evidence linking pantethine to neurodegeneration. PKAN represents the most logical disease context for pantethine investigation because impaired CoA biosynthesis is proximal to disease pathogenesis, although pantethine remains investigational and its clinical efficacy has not been established. By contrast, proposed applications in AD and PD remain highly theoretical and hypothesis-generating. Nevertheless, research on pantethine and related CoA-restoring strategies may identify new intervention targets across neurodegenerative diseases and other disorders characterized by impaired cellular bioenergetics, including selected neuropsychiatric disorders. These possibilities require biomarker-informed, disease-specific studies that establish active-species exposure, target engagement, and clinically meaningful effects.
Key findings
- Neurodegenerative diseases are a growing global health burden associated with aging and characterized by progressive neuronal dysfunction, metabolic failure, mitochondrial impairment, oxidative stress, and chronic neuroinflammation.
Study details
- Study designnarrative review
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Preprints.org) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 0 / 12 | Design recorded as “narrative review”, which our rubric does not rank (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Garcia Simili, O. A., Magno de Carvalho, G., Santana Dias Simões, R., Rucco Penteado Detregiachi, C., de Souza Bastos Mazuqueli Pereira, E., Cavallari Strozze Catharin, V. M., et al. (2026). Pantethine and Neurodegeneration: A Coenzyme A-Centered Framework Linking Metabolism, Neuroinflammation, and Mitochondrial Dysfunction. Preprints.org. https://doi.org/10.20944/preprints202607.2061.v5
Vancouver
Garcia Simili OA, Magno de Carvalho G, Santana Dias Simões R, Rucco Penteado Detregiachi C, de Souza Bastos Mazuqueli Pereira E, Cavallari Strozze Catharin VM, et al. Pantethine and Neurodegeneration: A Coenzyme A-Centered Framework Linking Metabolism, Neuroinflammation, and Mitochondrial Dysfunction. Preprints.org. 2026. doi:10.20944/preprints202607.2061.v5.
BibTeX
@article{garciasimili2026-9dc141d1,
author = {Garcia Simili, O. A. and Magno de Carvalho, G. and Santana Dias Simões, R. and Rucco Penteado Detregiachi, C. and de Souza Bastos Mazuqueli Pereira, E. and Cavallari Strozze Catharin, V. M. and da Silva, G. A. and Miola, V. B. and others},
title = {{Pantethine and Neurodegeneration: A Coenzyme A-Centered Framework Linking Metabolism, Neuroinflammation, and Mitochondrial Dysfunction}},
journal = {Preprints.org},
year = {2026},
doi = {10.20944/preprints202607.2061.v5},
url = {https://doi.org/10.20944/preprints202607.2061.v5}
}
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