Dual role of nitric oxide in Alzheimer's disease

Elsevier, Nitric Oxide - Biology and Chemistry, Volume 134-135, 1 May 2023
Azargoonjahromi A.

Nitric oxide (NO), an enzymatic product of nitric oxide synthase (NOS), has been associated with a variety of neurological diseases such as Alzheimer's disease (AD). NO has long been thought to contribute to neurotoxic insults caused by neuroinflammation in AD. This perception shifts as more attention is paid to the early stages before cognitive problems manifest. However, it has revealed a compensatory neuroprotective role for NO that protects synapses by increasing neuronal excitability. NO can positively affect neurons by inducing neuroplasticity, neuroprotection, and myelination, as well as having cytolytic activity to reduce inflammation. NO can also induce long-term potentiation (LTP), a process by which synaptic connections among neurons become more potent. Not to mention that such functions give rise to AD protection. Notably, it is unquestionably necessary to conduct more research to clarify NO pathways in neurodegenerative dementias because doing so could help us better understand their pathophysiology and develop more effective treatment options. All these findings bring us to the prevailing notion that NO can be used either as a therapeutic agent in patients afflicted with AD and other memory impairment disorders or as a contributor to the neurotoxic and aggressive factor in AD. In this review, after presenting a general background on AD and NO, various factors that have a pivotal role in both protecting and exacerbating AD and their correlation with NO will be elucidated. Following this, both the neuroprotective and neurotoxic effects of NO on neurons and glial cells among AD cases will be discussed in detail.