Work

Autosomal dominant neuronal ceroid lipofuscinosis: Clinical features and molecular basis

Year: 2020

Type: article

Abstract: The neuronal ceroid lipofuscinoses (NCLs) are at least 13 distinct progressive neurodegenerative disorders unified by the accumulation of lysosomal auto-fluorescent material called lipofuscin. The only form that occurs via autosomal-dominant inheritance exhibits adult onset and is sometimes referred to as Parry type NCL. The manifestations may include behavioral symptoms followed by seizures, ataxia, dementia, and early death. Mutations in the gene DNAJC5 that codes for the presynaptic co-chaperone cysteine string protein-α (CSPα) were recently reported in sporadic adult-onset cases and in families with dominant inheritance. The mutant CSPα protein may lead to disease progression by both loss and gain of function mechanisms. Iron chelation therapy may be considered as a possible pharmaceutical intervention based on our recent mechanism-based proposal of CSPα oligomerization via ectopic Fe-S cluster-binding, summarized in this review.

Source: Clinical Genetics

DOI: 10.1111/cge.13829

Authors: Nima Naseri, Manu Sharma, Milen Velinov

Institution: Weill Cornell Medicine

Language: English

Topic: Lysosomal Storage Disorders Research

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institute on Aging, National Institute of Neurological Disorders and Stroke