Astrocyte mediated MMP-9 activation in the synapse dysfunction: An implication in Alzheimer disease

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that occurs due to spasms of the neurons, resulting in loss of memory and behavioral changes. In particular, synaptic loss has been described as an early event in the pathogenesis of AD. The increasing evidences have suggested the role of many matrix metalloproteinase (MMPs) in central nervous system (CNS) pathology. Many studies showed that MMPs enzymes are important for the pathophysiological process during Alzheimer's disease (AD). It is usually believed that the synaptic dysfunction and synapse loss contribute to the cognitive deficits of patients with AD. Cerebrovascular events such as blood-brain barrier (BBB) disruption lead to neuronal damage as well as neuroinflammation. BBB dysfunctions are observed at an early post injury time point, and are associated with activation of proteases, such as MMPs especially MMP-9 which is actively engage in a neuronal injury in the most of the neurodegenerative disorders. BBB opening is accompanied by astrocytic activation, BBB injury and dysregulation of cerebral blood flow. Activated MMPs disrupt neurovascular unit (NVU) which may starve the neurons and affect the synapse function by altering synaptic plasticity and ultimately lead to cognitive decline. However, how MMPs implicated in synaptic dysfunction what are the mechanism associated with this disparity needs to discuss for better understanding the role of MMP-9 in pathogenesis of AD. In this review, we focused on the role of astrocytes and MMP-9 in synaptic dysfunction. We also, underlined possible pharmacological strategies for drug development that might offer more insight into the pathogenesis of cerebrovascular disease such as stroke and Vascular dementia.