**4. Role of Neuroinflammation in the Onset of Neurodegeneration**

Recent studies have demonstrated a bridge between chronic inflammation and neurodegeneration. Apoptosis or programmed cell death and necrosis lead to neuronal cell death in the brain [81]. An increased burden of neurodegenerative conditions on the health care system and a lack of effective treatments available pose an urgent need to identify new drug targets. The most common feature that has been found in several neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease is chronic neuroinflammation. Glial cells have been identified as the mediators of neurodegeneration and are responsible for the onset and progression of these diseases.

Neuronal health is mainly monitored by the nervous system's immune cells, called microglia [82]. These cells are activated upon any injury to neurons or infections, which further produces proinflammatory factors (M1 phenotype) or anti-inflammatory factors (M2 phenotype). For a healthy functioning of the human brain, it is necessary to have the correct balance between anti-inflammatory mediators, which allow for the repair and healing of tissues, and proinflammatory mediators, which clear the cellular debris and misfolded protein aggregation is maintained [83]. The activation of microglia cells in Alzheimer's and Parkinson's disease is mainly tilted towards the M1 phenotype, which leads to an exaggeration of inflammation and accelerates the progression of the disease [84]. The new therapies for the management of neurodegeneration include induction of the M2 phenotype and deactivation of the M1 phenotype in the brain.

Astrocytes are another type of glial cells that are present in the brain and regulate the maintenance and maturation of neuronal cells. They are highly sensitive and respond to injury very quickly, as do microglia cells [85]. Depending upon their activation, they can be neuroprotective by stimulating repair and reducing inflammation or be neurotoxic by promoting inflammation and contributing to the death of neuronal cells. Activated astrocytes also act as a proinflammatory factor in Parkinson's disease and Alzheimer's disease [86]. Their role has been implicated in the breakdown of the blood–brain barrier, thereby encouraging the infiltration of immune cells into the brain, which increases neuronal death by excessive stimulation and impairment of the uptake of neurotransmitter glutamate. Another type of glial cell, called oligodendrocytes, also poses a significant role in neurodegeneration [87]. Oligodendrocytes form a sheath of myelin around the nerve fibers, which permits the efficient and rapid transmission of electrical impulses across neurons and thus induces signal transmission. Damage in these cells has been attributed to the progression of multiple sclerosis and other neurodegenerative diseases in which the immune system attacks oligodendrocytes and damages the myelin sheath, thereby reducing levels of myelin proteins in brain tissue [88].
