Scientists find misfolded neural protein linked to autism

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Scientists find misfolded neural protein linked to autism

Scientists have identified genetic misfolding in a key brain protein associated

with autism spectrum disorders (ASD), a finding that may lead to new treatment

for the psychological condition in children.

ASD causes severe and pervasive impairment in thinking, feeling, language, and

the ability to relate to others. These disorders are usually first diagnosed in

early childhood and range from a severe form, called autistic disorder.

An international team of scientists led by researchers at the University of

California found misfolding and other molecular anomalies caused by genetic

mutations in a protein called neuroligin-3.

This genetic misfolding, according to the researchers, results in trafficking

deficiencies that may lead to abnormal communications between neurons. The gene

mutation has been documented in patients with autism.

“It makes sense that there’s a connection,” said Palmer , associate vice

chancellor for Health Sciences at University of California.

“The neuroligins are involved in maintaining neuronal synapses and their

malfunction is likely to affect a neurodevelopmental disease,” said , who

led the study.

Neuroligins are post-synaptic proteins that help glue together neurons at

synapses by connecting with pre-synaptic protein partners called neurexins.

They are part of a larger family of alpha-beta-hydrolase fold proteins that

includes many molecules with diverse catalytic, adhesion and secretory

functions.

Using live neurons in culture, the researchers found that different mutations

caused different degrees of misfolding of the protein structure.

This translated into trafficking deficiencies of varying severity regardless of

alpha-beta-hydrolase protein type, yet resulted in distinctly different

congenital disorders in the endocrine or nervous systems.

said that identifying and describing the misfolded protein link advances

understanding of the complex causes of certain autisms, including the influences

of genes versus environment, and perhaps offers a new target for potential drug

therapies.

“If the mutation is identified early, it might be possible to rescue affected

neurons before abnormal synaptic connections are established” said co-author

e Comoletti, a research scientist at the Skaggs School of Pharmacy.

“But much work remains. We may be able to find a treatment to fix a cell in

culture, but to rescue function in vivo may not be feasible with the same

strategy.”

The new findings are appeared in the Journal of Biological Chemistry.