Shank synaptic scaffold proteins: keys to understanding the pathogenesis of autism and other synaptic disorders.
Shank/ProSAP proteins are essential to synaptic formation, development, and function. Mutations in the family of SHANK genes are strongly associated with autism spectrum disorders (ASD) and other neurodevelopmental and neuropsychiatric disorders, such as intellectual disability (ID), and schizophrenia. Thus, the term 'Shankopathies' identifies a number of neuronal diseases caused by alteration of Shank protein expression leading to abnormal synaptic development. With this review we want to summarize the major genetic, molecular, behavior and electrophysiological studies that provide new clues into the function of Shanks and pave the way for the discovery of new therapeutic drugs targeted to treat patients with SHANK mutations and also patients affected by other neurodevelopmental and neuropsychiatric disorders. Shank/ProSAP proteins are essential to synaptic formation, development, and function. Mutations in the family of SHANK genes are strongly associated with autism spectrum disorders (ASD) and other neurodevelopmental and neuropsychiatric disorders, such as intellectual disability (ID), and schizophrenia (SCZ). With this review we want to summarize the major genetic, molecular, behavior and electrophysiological studies that provide new clues into the function of Shanks and pave the way for the discovery of new therapeutic drugs targeted to treat patients with SHANK mutations.
CNR Neuroscience Institute and Department of Biotechnology and Translational Medicine, University of Milan, Milan, Italy.
Carlo
C
Sala
CNR Neuroscience Institute and Department of Biotechnology and Translational Medicine, University of Milan, Milan, Italy.
Cinzia
C
Vicidomini
CNR Neuroscience Institute and Department of Biotechnology and Translational Medicine, University of Milan, Milan, Italy.
Ilaria
I
Bigi
CNR Neuroscience Institute and Department of Biotechnology and Translational Medicine, University of Milan, Milan, Italy.
Adele
A
Mossa
CNR Neuroscience Institute and Department of Biotechnology and Translational Medicine, University of Milan, Milan, Italy.
Chiara
C
Verpelli
D000818:Animals; D001321:Autistic Disorder / Q000235:genetics* / Q000473:pathology; D006801:Humans; D001523:Mental Disorders / Q000235:genetics / Q000473:pathology; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D065886:Neurodevelopmental Disorders / Q000235:genetics* / Q000473:pathology; D013569:Synapses / Q000235:genetics / Q000473:pathology*
D009419:Nerve Tissue Proteins; C122162:SHANK2 protein, human
Phelan-McDemid syndrome; excitatory synapse; inhibitory synapse; intellectual disability; mouse models