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Review
. 2018 Mar 8:2018:3740461.
doi: 10.1155/2018/3740461. eCollection 2018.

Current Concepts of Neurodegenerative Mechanisms in Alzheimer's Disease

Kasthuri Bai Magalingam  1   2 , Ammu Radhakrishnan  1 , Ng Shee Ping  2 , Nagaraja Haleagrahara  3
Affiliations
Review

Current Concepts of Neurodegenerative Mechanisms in Alzheimer's Disease

Kasthuri Bai Magalingam et al. Biomed Res Int. .

Abstract

Neurodegenerative diseases are hereditary or sporadic conditions that result in the progressive loss of the structure and function of neurons as well as neuronal death. Although a range of diseases lie under this umbrella term, Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases that affect a large population around the globe. Alzheimer's disease is characterized by the abnormal accumulation of extracellular amyloid-β plaques and intraneuronal neurofibrillary tangles in brain regions and manifests as a type of dementia in aged individuals that results in memory loss, multiple cognitive abnormalities, and intellectual disabilities that interfere with quality of life. Since the discovery of AD, a wealth of new information has emerged that delineates the causes, mechanisms of disease, and potential therapeutic agents, but an effective remedy to cure the diseases has not been identified yet. This could be because of the complexity of the disease process, as it involves various contributing factors that include environmental factors and genetic predispositions. This review summarizes the current understanding on neurodegenerative mechanisms that lead to the emergence of the pathology of AD.

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Figures

Figure 1
Figure 1
Activated Nuclear Factor 2 (Nrf2) by oxidative stress enters nucleus and escalates the transcription of ARE-containing genes. These genes cause the expression of antioxidant enzymes, that is, SOD (superoxide dismutase), Glut (glutathione), GPx (glutathione peroxidase), CAT (catalase), and GST (reduced glutathione). Subsequently, these enzymes will catalyse the detoxification of ROS and protect neuronal cells from damage. Glycogen synthase kinase-3β participates in phosphorylation of tau protein and induce accumulation of neurofibrillary tangles (NFT) that inhibits Nrf2. Besides inhibiting NRf2 activity, alpha-synuclein and NFT stimulate oxidative stress via ROS production.
Figure 2
Figure 2
Protein degradation by ubiquitin-proteasome pathway. E1, E2, and E3-ubiquitinating enzymes.
See this image and copyright information in PMC

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