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Modeling spastic paraplegia 4 with corticospinal motor neuron-enriched cortical organoids reveals genotype-phenotype and HDAC6-targetable pathology.

Cell reports - 24 Mar 2026

Mohan Neha, Ramakrishnan Skandha, Sun Xiaohuan, Sun Ying, Connors Theresa, Chai Victor, Piermarini Emanuela, Baas Peter W, Cai James, Liu Mei, Qiang Liang

Abstract excerpt

Spastic paraplegia 4 (SPG4), the most common form of hereditary spastic paraplegia, causes progressive gait deficiency due to corticospinal tract degeneration. SPG4 results from mutations in the SPAST gene, which encodes spastin, a microtubule-severing AAA-ATPase. To dissect genotype-phenotype relationships, we generated isogenic human induced pluripotent stem cell lines carrying either an SPAST missense...

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Axons
Hydroxamic Acids
Microtubules
Motor Neurons
Organoids

Methodology Data sources Editorial policy Privacy About Contact Helena Bioinformatics

Pyramidal Tracts

Spastic Paraplegia, Hereditary

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Identifiers

PMID: 41739645
DOI: 10.1016/j.celrep.2026.117036
PMCID: PMC13076005

Genes

HDAC6
SPAST

Variants

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PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 31 Aug 2026.

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Modeling spastic paraplegia 4 with corticospinal motor neuron-enriched cortical organoids reveals genotype-phenotype and HDAC6-targetable pathology.PMID 41739645Read ↗

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