Neuroinflammation to neurodegeneration: Boulevard of broken nerves

Neuroinflammation is caused by various factors, such as the activation of glial cells, the excessive release of chemokines and cytokines, and the accumulation of blood cells in the brain parenchyma. The inflammatory processes occur in acute and chronic phases, with traumatic brain injuries triggering the release of neurotoxins from CNS-specific glial cells. Furthermore, activation of microglia, astrocytes, and mast cells worsens the situation by producing pro-inflammatory cytokines, chemokines and glia maturation factors. Chronic activation of astroglia and microglial cells promotes loss of neurons, memory, and impaired learning capacity, leading to neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. These implications have led to a rational search for inflammatory druggable targets. Based on various preclinical and clinical studies, NSAIDs (aspirin, ibuprofen, diclofenac, and mefenamic acid), SSRIs (fluoxetine and sertraline), antipsychotics (risperidone), corticosteroids (dexamethasone), antidiabetics (metformin and rosiglitazone), and statins (simvastatin and atorvastatin) have exhibited promising results. These drugs have anti-inflammatory and neuromodulation activities that enhance neuroplasticity and effectively manage neurodegenerative symptoms. In addition, non-pharmacological interventions such as art creation and physical exercise have been linked with improving neural development and stimulating the production of anti-inflammatory cytokines, which can attenuate disease progression and promote synaptic plasticity. Hence, it is imperative to understand the complex interplay between glial cells, inflammatory signalling and neural pathways. We reviewed the interconnected pathways between neuroinflammation and neurodegeneration. Moreover, recommendations for pharmacological and non-pharmacological interventions to address these issues are discussed herein.