**2. Neurodegenerative diseases and their impact**

Essentially, the CNS must be protected from oxidative stress, induced majorly by ROS, with both endogenous and non-endogenous defense systems. The role of endogenous and exogenous antioxidant systems in CNS has been well-reviewed [15]. For example, endogenous enzymatic antioxidants activity in CNS, the superoxide dismutase (SOD) reduces oxidative stress, tau hyperphosphorylation and apoptosis [16] glutathione peroxidase (GPx) induces neuroprotection and activate ferroptosis [17] glutathione synthase (GST) increase the level of GSTα4 for neuroprotection [18] and glutathione (GSH) a non- enzymatic endogenous antioxidant increase GSH/ GS-SG to prevent neurodegeneration [19].

NDs are a constellation of disease conditions that are often progressive, chronic, and devastating that affect or induce neurons of the peripheral and central nervous system to be defective. This results to reduce neurons or loss of their activity and integrity (protein tangling and aggregation), loss or lack of transmission or communication, and hence cognitive loss, as well as loss or lack of motor and sensory functions [20–22]. In other words, neurodegeneration indicates both loss of structure and function of neurons, attributed as the hallmark of most NDs. Although the genesis of most NDs is not definitive or clear, neurodegeneration and neuroinflammation linked to oxidative stress alter the homeostasis of the CNS with various aforementioned pathological characteristics associated with NDs. The possible shared pathophysiology or mechanism of most NDs include oxidative stress, neuroinflammation, autophagy, altered cellular energetics, and calcium overload, among others are attributed to the pathogenesis of PD, AD, ALS, MS, HD, Friedreich's ataxia spinal muscular atrophy, etc.
