Unveiling the modulation of Nogo receptor in neuroregeneration and plasticity: Novel aspects and future horizon in a new frontier.

Neurodegenerative diseases (NDs) such as Alzheimer's, Parkinson's, Multiple Sclerosis, Hereditary Spastic Paraplegia, and Amyotrophic Lateral Sclerosis have emerged as the most dreaded diseases due to a lack of precise diagnostic tools and efficient therapies. Despite the fact that the contributing factors of NDs are still unidentified, mounting evidence indicates the possibility that genetic and cellular changes may lead to the significant production of abnormally misfolded proteins. These misfolded proteins lead to damaging effects thereby causing neurodegeneration. The association between Neurite outgrowth factor (Nogo) with neurological diseases and other peripheral diseases is coming into play. Three isoforms of Nogo have been identified Nogo-A, Nogo-B and Nogo-C. Among these, Nogo-A is mainly responsible for neurological diseases as it is localized in the CNS (Central Nervous System), whereas Nogo-B and Nogo-C are responsible for other diseases such as colitis, lung, intestinal injury, etc. Nogo-A, a membrane protein, had first been described as a CNS-specific inhibitor of axonal regeneration. Several recent studies have revealed the role of Nogo-A proteins and their receptors in modulating neurite outgrowth, branching, and precursor migration during nervous system development. It may also modulate or affect the inhibition of growth during the developmental processes of the CNS. Information about the effects of other ligands of Nogo protein on the CNS are yet to be discovered however several pieces of evidence have suggested that it may also influence the neuronal maturation of CNS and targeting Nogo-A could prove to be beneficial in several neurodegenerative diseases.

Emerging Pathophysiological Mechanisms Linking Diabetes Mellitus and Alzheimer's Disease: An Old Wine in a New Bottle.

Type-2 diabetes mellitus (T2DM) is a chronic immuno-inflammatory and metabolic disease characterized by hyperglycemia and insulin resistance with corresponding hyperinsulinemia. On the other hand, Alzheimer's disease (AD) is a neurodegenerative disease involving cognitive impairment, neuronal dysfunction, and memory loss. Several recently published literatures suggest a causal relationship between T2DM and AD. In this review, we have discussed several potential mechanisms underlying diabetes-induced cognitive impairment which include, abnormal insulin signaling, amyloid-ß accumulation, oxidative stress, immuno-inflammation, mitochondrial dysfunction, advanced glycation end products, acetylcholinesterase and butyrylcholinesterase, advanced lipid peroxidation products, and apolipoprotein E. All these interconnected mechanisms may act either individually or synergistically which eventually leads to neurodegeneration and AD.