Trends in the molecular pathogenesis and clinical therapeutics of common neurodegenerative disorders

Abstract

The term neurodegenerative disorders, encompasses a variety of underlying conditions, sporadic and/or familial and are characterized by the persistent loss of neuronal subtypes. These disorders can disrupt molecular pathways, synapses, neuronal subpopulations and local circuits in specific brain regions, as well as higher-order neural networks. Abnormal network activities may result in a vicious cycle, further impairing the integrity and functions of neurons and synapses, for example, through aberrant excitation or inhibition. The most common neurodegenerative disorders are Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis and Huntington's disease. The molecular features of these disorders have been extensively researched and various unique neurotherapeutic interventions have been developed. However, there is an enormous coercion to integrate the existing knowledge in order to intensify the reliability with which neurodegenerative disorders can be diagnosed and treated. The objective of this review article is therefore to assimilate these disorders' in terms of their neuropathology, neurogenetics, etiology, trends in pharmacological treatment, clinical management, and the use of innovative neurotherapeutic interventions.

Keywords: Alzheimer’s disease; Amyotrophic Lateral Sclerosis; Huntingtin; Huntington’s disease; Parkinson’s disease; Tau; amyloid-β protein; drug delivery; neuropathology; neurotherapeutics; α-Synuclein.

Figure 1.

Schematic diagram outlining the pathogenesis of common neurodegenerative diseases (Adapted from Yuan and Yanker, [16]).

Figure 2.

The role of glial cells in central nervous system inflammation and neurodegeneration. BDNF = brain-derived neurotrophic factor, MP = macrophages, MMP = membrane metalloproteinase, TIMP = tissue inhibitors of metalloproteinase (Adapted from: Ghorpade et al. [113]).

Figure 3.

Molecular mechanisms leading to cell death in neurons and the yeast PD model (Adapted from: Winderickx et al. [164]).

Figure 4.

Depiction of adult neural stem demonstrating their intrinsic potential to generate cell types of the brain and spinal cord (Adapted from: Karimi and Eftekharpour, Fehlings lab, McEwan Centre for Regnerative Medicine; www.mcewencentre.com/res_prog_scnd.asp, [182]).

Figure 5.

Schematic of SOD-1 mutations activating cell death pathways in familial Amyotrophic Lateral Sclerosis (Source: Yuan and Yankner, [16]).

Figure 6.

Schematic depicting a pathway of oxidative damage in HD (Source: Trushina and McMurray, [232]).

Figure 7.

A minimally-invasive intrathecal drug delivery system for spinal cord injury repair (Source: Shoichet lab, McEwen Centre for Regenerative Medicine, [276]).