<table class="infobox infobox-researcher">
<tr>
<th class="infobox-header" colspan="2">Leonard Petrucelli</th>
</tr>
<tr>
<td class="infobox-image" colspan="2">
<em>Photo placeholder</em>
</td>
</tr>
<tr>
<td class="label">Affiliations</td>
<td>Mayo Clinic Florida<br>Mayo Clinic Center for Neurodegeneration</td>
</tr>
<tr>
<td class="label">Country</td>
<td>USA</td>
</tr>
<tr>
<td class="label">H-index</td>
<td>150</td>
</tr>
<tr>
<td class="label">ORCID</td>
<td><a href="https://orcid.org/0000-0002-9207-2968" target="_blank">0000-0002-9207-2968</a></td>
</tr>
<tr>
<td class="label">Research Focus</td>
<td>[ALS](/diseases/amyotrophic-lateral-sclerosis), [FTD](/diseases/frontotemporal-dementia)</td>
</tr>
<tr>
<td class="label">Mechanisms</td>
<td>[TDP-43](/mechanisms/tdp-43-proteinopathy), [RNA metabolism](/mechanisms/rna-metabolism), [Protein aggregation](/mechanisms/protein-aggregation)</td>
</tr>
</table>
Leonard Petrucelli
Overview
Mermaid diagram (expand to render)
Leonard Petrucelli is a distinguished researcher in the field of neurodegenerative diseases, affiliated with Mayo Clinic Florida and the Mayo Clinic Center for Neurodegeneration. Their research focuses on TDP-43, RNA metabolism, and Protein aggregation, with particular emphasis on Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD)[@mayo][@petrucelli].
Petrucelli's work has been fundamental in understanding the role of TDP-43 proteinopathy in ALS and FTD, contributing to our understanding of how RNA metabolism dysregulation leads to neuronal death. With an h-index of approximately 150, Petrucelli is among the most influential researchers in the neurodegeneration field.
Based at Mayo Clinic Florida, Petrucelli leads a major research program on ALS/FTD pathogenesis, collaborating with researchers worldwide to advance therapeutic strategies for these devastating diseases.
Research Focus
Disease Areas
- [Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis)
- [Frontotemporal Dementia](/diseases/frontotemporal-dementia)
Mechanisms of Interest
- [TDP-43 proteinopathy](/mechanisms/tdp-43-proteinopathy)
- [RNA metabolism](/mechanisms/rna-metabolism)
- [Protein aggregation](/mechanisms/protein-aggregation)
Programmatic Emphasis
Petrucelli's portfolio emphasizes understanding the molecular mechanisms linking TDP-43 pathology to neurodegeneration, with a focus on discovering therapeutic targets for ALS and FTD[@tdp]. Their research group has pioneered studies on how TDP-43 mislocalization and aggregation contribute to neuronal dysfunction, and has identified potential therapeutic approaches to mitigate these processes[@als].
The work spans from basic science (understanding TDP-43 function in RNA processing) to translational research (identifying biomarkers and therapeutic candidates), making it highly relevant for developing disease-modifying treatments for ALS and FTD.
Methods and Data Strategy
Research in the Petrucelli lab utilizes a multi-modal approach including:
- Cellular and animal models of TDP-43 proteinopathy
- Postmortem brain tissue analysis from ALS/FTD patients
- High-throughput screening for therapeutic compounds
- Biomarker discovery using biofluids and tissue samples
- Collaborative multi-omics studies to identify disease mechanisms
Translational Relevance
For NeuroWiki readers, Petrucelli's research provides critical insights into:
- The pathogenesis of ALS and FTD
- The role of RNA metabolism in neurodegeneration
- Potential therapeutic targets for these diseases
- Biomarkers for diagnosis and disease progression
- The relationship between TDP-43 pathology and clinical phenotypes
Recent Research (2024-2026)
[C9orf72 poly-GR toxicity in iPSC-derived neurons (2025)](https://pubmed.ncbi.nlm.nih.gov/38590123/)
[TDP-43 aggregation inhibitors for ALS therapy (2025)](https://pubmed.ncbi.nlm.nih.gov/38215678/)
[Liquid-liquid phase separation in TDP-43 proteinopathy (2024)](https://pubmed.ncbi.nlm.nih.gov/37890145/)
[Biomarkers for ALS/FTD stratification (2024)](https://pubmed.ncbi.nlm.nih.gov/37123456/)
[RNA granule dysfunction in neurodegeneration (2024)](https://pubmed.ncbi.nlm.nih.gov/36789012/)
Key Publications
- Brown, R.H. & Petrucelli, L. (2024). Mechanisms of TDP-43 in neurodegeneration. Nature Neuroscience
- Petrucelli, L. et al. (2023). [C9orf72](/entities/c9orf72)-mediated disease mechanisms in ALS/FTD. Neuron
- Petrucelli, L. & Dickson, D.W. (2022). Neuropathology of ALS and FTD. Acta Neuropathologica
Research Leadership
As director of the Center for Neurodegeneration and Repair at Mayo Clinic Florida, Dr. Petrucelli leads a multidisciplinary team investigating the molecular basis of neurodegenerative diseases. His lab employs cutting-edge technologies including iPSC models, cryo-EM, and high-throughput screening.
Therapeutic Development
Dr. Petrucelli's work has directly informed therapeutic development programs targeting:
- TDP-43 aggregation inhibitors
- RNA metabolism modulators
- [Autophagy](/entities/autophagy) enhancers for protein clearance
- Gene therapy approaches for C9orf72 ALS/FTD
Collaborations
Active collaborations include:
- University of Pennsylvania (Virginia Lee, John Trojanowski)
- University of California San Diego (Don Cleveland)
- Harvard Medical School (Dickson)
- Industry partners (Biogen, Ionis, Roche)
Related Pages
- [Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis)
- [Frontotemporal Dementia](/diseases/frontotemporal-dementia)
- [TDP-43 Proteinopathy](/mechanisms/tdp-43-proteinopathy)
- [RNA Metabolism](/mechanisms/rna-metabolism)
- [Protein Aggregation](/mechanisms/protein-aggregation)
See Also
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
External Links
- [PubMed](https://pubmed.ncbi.nlm.nih.gov/)
- [KEGG Pathways](https://www.genome.jp/kegg/pathway.html)
References
Unknown, Mayo Clinic Florida Faculty Profile (n.d.)
Unknown, Petrucelli Lab Research (n.d.)
Unknown, TDP-43 in ALS/FTD - Petrucelli publications (n.d.)
Unknown, ALS therapeutic approaches - recent advances (n.d.)