Neuronal Polarity and Neurological Disorders

Neuronal cell function is largely dependent on polarity. Studies in the past decades indicate that the neuronal polarity machinery is one of the major targets of neurological disorders. Planar cell polarity (PCP) and apicobasal (AB) polarity modules were shown to be crucial for the establishment of neuronal polarity. Accordingly, neural tube defects (NTDs) have been associated with mutations in several polarity genes [1]. Similarly, genetic screening has identified several mutated genes that are associated with dysfunction of cytoskeletal components in Alzheimer’s disease (AD) and Parkinson’s disease (PD). Downstream of the polarity pathways, aggregations of misregulated cytoskeletal products are frequently observed in hereditary familial diseases such as AD and PD. Nonetheless, disruption of neuronal polarity-related cell functions including protein transportation and synaptic connections constitutes the main cause for the abnormal neural development and/ or neuronal loss. As such, restoration of neuronal polarity in neurodegenerative diseases would potentially slow down or prevent neuronal degeneration over time.