Physiological and pathophysiological functions of cell cycle proteins in post-mitotic neurons: implications for...

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder for which no effective treatment is available. Increased insight into the disease mechanism in early stages of pathology is required for the development of a successful therapy. Over the years, numerous studies have shown that cell cycle proteins are expressed in neurons of AD patients. Traditionally, neurons are considered to be post-mitotic, which means that they permanently retract from the cell cycle. The expression of cell cycle proteins in adult neurons of AD patients has therefore been suggested to promote or even instigate pathomechanisms underlying AD. Interestingly, expression of cell cycle proteins is detected in post-mitotic neurons of healthy controls as well, albeit to a lesser extent than in AD patients. This indicates that cell cycle proteins may serve important physiological functions in differentiated neurons. Here, we provide an overview of studies that support a role of cell cycle proteins in DNA repair and neuroplasticity in post-mitotic neurons. Aberrant control of these processes could, in turn, contribute to cell cycle-mediated neurodegeneration. The balance between regenerative and degenerative effects of cell cycle proteins in post-mitotic neurons might change throughout the different stages of AD. In the early stages of AD pathology, cell cycle protein expression may primarily occur to aid in the repair of sublethal double-strand breaks in DNA. With the accumulation of pathology, cell cycle-mediated neuroplasticity and neurodegeneration may become more predominant. Understanding the physiological and pathophysiological role of cell cycle proteins in AD could give us more insight into the neurodegenerative process in AD.