Emerging Connections between Nuclear Pore Complex Homeostasis and ALS
| Autor: | C. Patrick Lusk, Sunandini Chandra |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Motor Neurons
QH301-705.5 Amyotrophic Lateral Sclerosis Organic Chemistry CHMP7 Active Transport Cell Nucleus General Medicine nuclear transport Catalysis Computer Science Applications ESCRT Inorganic Chemistry Chemistry Nuclear Pore Homeostasis Humans Physical and Theoretical Chemistry Biology (General) POM121 Molecular Biology QD1-999 Spectroscopy NPC injury C9ORF72 ALS |
| Zdroj: | International Journal of Molecular Sciences, Vol 23, Iss 1329, p 1329 (2022) |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | Developing effective treatments for neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) requires understanding of the underlying pathomechanisms that contribute to the motor neuron loss that defines the disease. As it causes the largest fraction of familial ALS cases, considerable effort has focused on hexanucleotide repeat expansions in the C9ORF72 gene, which encode toxic repeat RNA and dipeptide repeat (DPR) proteins. Both the repeat RNA and DPRs interact with and perturb multiple elements of the nuclear transport machinery, including shuttling nuclear transport receptors, the Ran GTPase and the nucleoporin proteins (nups) that build the nuclear pore complex (NPC). Here, we consider recent work that describes changes to the molecular composition of the NPC in C9ORF72 model and patient neurons in the context of quality control mechanisms that function at the nuclear envelope (NE). For example, changes to NPC structure may be caused by the dysregulation of a conserved NE surveillance pathway mediated by the endosomal sorting complexes required for the transport protein, CHMP7. Thus, these studies are introducing NE and NPC quality control pathways as key elements in a pathological cascade that leads to C9ORF72 ALS, opening entirely new experimental avenues and possibilities for targeted therapeutic intervention. |
| Databáze: | OpenAIRE |
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