Expression profiles of the autism-related SHANK proteins in the human brain.

Background: SHANKs are major scaffolding proteins at postsynaptic densities (PSDs) in the central nervous system. Mutations in all three family members have been associated with neurodevelopmental disorders such as autism spectrum disorders (ASDs). Despite the pathophysiological importance of SHANK2 and SHANK3 mutations in humans, research on the expression of these proteins is mostly based on rodent model organisms.

CLARITY increases sensitivity and specificity of fluorescence immunostaining in long-term archived human brain tissue.

Background: Post mortem human brain tissue is an essential resource to study cell types, connectivity as well as subcellular structures down to the molecular setup of the central nervous system especially with respect to the plethora of brain diseases. A key method is immunostaining with fluorescent dyes, which allows high-resolution imaging in three dimensions of multiple structures simultaneously. Although there are large collections of formalin-fixed brains, research is often limited because several conditions arise that complicate the use of human brain tissue for high-resolution fluorescence microscopy.

Cerebellar and Striatal Pathologies in Mouse Models of Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a strong genetic component. To date, several hundred different genetic mutations have been identified to play a role in its aetiology. The heterogeneity of genetic abnormalities combined with the different brain regions where aberrations are found makes the search for causative mechanisms a daunting task.

Genetic Animal Models for Autism Spectrum Disorder.

Autism spectrum disorder (ASD) affects approximately 1 % of the human population and has a strong genetic component. Hence, the recent discovery of major "ASD genes" has subsequently resulted in the generation of several genetic animal models of ASD. Careful analysis of behavioral phenotypes and characterization of the underlying neurobiological mechanisms in these models should further help us to identify novel therapeutic targets and develop more effective strategies in the future to ameliorate or even reverse core symptoms and comorbidities of ASD.

ProSAP-interacting protein 1 (ProSAPiP1), a novel protein of the postsynaptic density that links the spine-associated Rap-Gap (SPAR) to the scaffolding protein ProSAP2/Shank3.

ProSAPs/Shanks are a family of proteins that have a major scaffolding function for components of the postsynaptic density (PSD) of excitatory brain synapses. Members of the family harbor a variety of domains for protein-protein interactions, one of which is a unique PDZ domain that differs significantly from those of other proteins. We have identified a novel binding partner for this PDZ domain, termed ProSAPiP1, that is highly enriched in the PSD and shares significant sequence homology with the PSD protein PSD-Zip70.