首页|Spastin and alsin protein interactome analyses begin to reveal key canonical pathways and suggest novel druggable targets

Spastin and alsin protein interactome analyses begin to reveal key canonical pathways and suggest novel druggable targets

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Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging.One of the major roadblocks is the extensive heterogeneity among patients.This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients.One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients.Especially in patients with a known genetic mutation,it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration.Protein-protein interaction analyses offer great advantages for revealing how proteins interact,which cellular events are primarily involved in these interactions,and how they become affected when key genes are mutated in patients.This line of investigation also suggests novel druggable targets for patients with different mutations.Here,we focus on alsin and spastin,two proteins that are identified as"causative"for amyotrophic lateral sclerosis and hereditary spastic paraplegia,respectively,when mutated.Our review analyzes the protein interactome for alsin and spastin,the canonical pathways that are primarily important for each protein domain,as well as compounds that are either Food and Drug Administration-approved or are in active clinical trials concerning the affected cellular pathways.This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.

ALS2alsinamyotrophic lateral sclerosishereditary spastic paraplegianeurodegenerative diseasespersonalized medicineprecision medicineprotein interactomeprotein-protein interactionsSPASTspastin

Benjamin R.Helmold、Angela Ahrens、Zachary Fitzgerald、P.Hande Ozdinler

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Department of Neurology,Feinberg School of Medicine,Northwestern University,Chicago,IL,USA

Center for Molecular Innovation and Drug Discovery,Center for Developmental Therapeutics,Chemistry of Life Processes Institute,Northwestern University,Evanston,IL,USA

Mesulam Center for Cognitive Neurology and Alzheimer's Disease,Feinberg School of Medicine,Northwestern University,Chicago,IL,USA

Feinberg School of Medicine,Les Turner ALS Center at Northwestern University,Chicago,IL,USA

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2025

中国神经再生研究(英文版)
中国康复医学会

中国神经再生研究(英文版)

影响因子:0.902
ISSN:1673-5374
年,卷(期):2025.20(3)