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Molecular basis of infantile Batten disease: impact of disordered palmitoylated protein degradation on the nervous system (466.1)
Author(s) -
Hofmann Sandra,
Lu JuiYun
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.466.1
Subject(s) - palmitoylation , batten disease , neuronal ceroid lipofuscinosis , substrate reduction therapy , enzyme replacement therapy , transplantation , nervous system , lysosome , neuroscience , biology , medicine , chemistry , enzyme , disease , biochemistry , cysteine
S ‐palmitoylation (or more generally, S‐fatty acylation) is a common cysteine modification of proteins that plays key roles in protein stability, protein‐protein and protein‐membrane interaction. Palmitoylated proteins are abundant in neuronal cells. A final pathway for palmitoylated protein degradation involves an enzyme, palmitoyl‐protein thioesterase (PPT1), a specialized lipase of the lysosome. An inborn error of metabolism, infantile neuronal ceroid lipofuscinosis (also known as infantile Batten Disease), results from PPT1 deficiency and the subsequent inability to degrade palmitoylated proteins. Severely affected children are normal to the age of 12‐18 months, after which they display cognitive and motor regression, seizures, and blindness. Partial deficiencies may result in psychiatric manifestations and dementia. Over 60 mutations have been described. Treatment approaches have included bone marrow transplantation, substrate reduction, and neural stem cell transplantation but these have been unsuccessful thus far. Enzyme replacement therapy, which may be beneficial for visceral manifestations of the disease, is in preclinical development, and ways to deliver enzyme to the central nervous system are being sought. Improved understanding of protein palmitoyltransferases and their substrates in the nervous system is expected lead to treatment for this and related disorders.