Abstract
During brain development, neurons need to form the correct connections with one another in order to give rise to a functional neuronal circuitry. Mistakes during this process, leading to the formation of improper neuronal connectivity, can result in a number of brain abnormalities and impairments collectively referred to as neurodevelopmental disorders. Cell adhesion molecules (CAMs), present on the cell surface, take part in the neurodevelopmental process regulating migration and recognition of specific cells to form functional neuronal assemblies. Among CAMs, the members of the protocadherin (PCDH) group stand out because they are involved in cell adhesion, neurite initiation and outgrowth, axon pathfinding and fasciculation, and synapse formation and stabilization. Given the critical role of these macromolecules in the major neurodevelopmental processes, it is not surprising that clinical and basic research in the past two decades has identified several PCDH genes as responsible for a large fraction of neurodevelopmental disorders. In the present article, we review these findings with a focus on the non-clustered PCDH sub-group, discussing the proteins implicated in the main neurodevelopmental disorders.
Highlights
Neurodevelopmental disorders are a group of diseases occurring in early life and characterized by a significant alteration of the central nervous system (CNS) functioning, resulting in the failure to meet the typical developmental milestones
PCDHs have been implicated in several neurodevelopmental disorders such as the outgrowth of the striatal axons [46,48], the absence of PCDH17 has been considered determinant intellectual disability (ID), epilepsy, Fragile-X syndrome (FXS), and Autism spectrum disorders in causing defects in the extension of axons from specific subdivisions of the amygdala
PCDHs have been implicated in several neurodevelopmental disorders such as intellectual disability (ID), epilepsy, Fragile-X syndrome (FXS), and Autism spectrum disorders (ASDs) and have been demonstrated to fulfill roles in disease states conceptualized as neurodevelopmental disorders including schizophrenia (SZ) and bipolar disorder (BD) (Table 2)
Summary
Neurodevelopmental disorders are a group of diseases occurring in early life and characterized by a significant alteration of the central nervous system (CNS) functioning, resulting in the failure to meet the typical developmental milestones. Brain dysfunction can manifest in several different ways ranging from intellectual alterations and problems of learning and communication to motor function impairment. The different disorders have a heterogeneous etiology, there is often overlap of symptomatology between the numerous neurodevelopmental disorders [1,2], and association with many co-morbidities including epilepsy, mood disorders, impairment in vision and hearing, sleep disturbances, and gastrointestinal and breathing problems. Many studies have suggested that shared molecular pathways could account for the multiple clinical signs that characterize these diseases [3]. The altered sociability, often observed in individuals with neurodevelopmental disorders, makes such diseases a significant and expanding public health problem. We will focus on selected non-clustered PCDHs discussing their implication in neurodevelopmental disorders
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