Neuroprotective and Therapeutic Strategies against Parkinson’s Disease: Recent Perspectives

Abstract

Parkinsonism is a progressive motor disease that affects 1.5 million Americans and is the second most common neurodegenerative disease after Alzheimer’s. Typical neuropathological features of Parkinson’s disease (PD) include degeneration of dopaminergic neurons located in the pars compacta of the substantia nigra that project to the striatum (nigro-striatal pathway) and depositions of cytoplasmic fibrillary inclusions (Lewy bodies) which contain ubiquitin and α-synuclein. The cardinal motor signs of PD are tremors, rigidity, slow movement (bradykinesia), poor balance, and difficulty in walking (Parkinsonian gait). In addition to motor symptoms, non-motor symptoms that include autonomic and psychiatric as well as cognitive impairments are pressing issues that need to be addressed. Several different mechanisms play an important role in generation of Lewy bodies; endoplasmic reticulum (ER) stress induced unfolded proteins, neuroinflammation and eventual loss of dopaminergic neurons in the substantia nigra of mid brain in PD. Moreover, these diverse processes that result in PD make modeling of the disease and evaluation of therapeutics against this devastating disease difficult. Here, we will discuss diverse mechanisms that are involved in PD, neuroprotective and therapeutic strategies currently in clinical trial or in preclinical stages, and impart views about strategies that are promising to mitigate PD pathology.

Prosodic Improvement in Persons with Parkinson Disease Receiving SPEAK OUT!® Voice Therapy

“…have PD, and about 60,000 Americans are newly diagnosed each year [1,2]. Fifty percent more men are affected than women [3].…”

Neuroprotective effects of selegiline on rat neural stem cells treated with hydrogen peroxide

“…Their etiologies remain uncertain, though there are a number of established pathogenic factors, including oxidative stress, neural apoptosis, mitochondrial dysfunction, excitotoxicity, impairment of the ubiquitin-proteasome system and inflammation (2,3). Neuroprotective therapy has been suggested to prevent disease progression by inhibiting the action of pathogenic factors, for instance, by reducing the production of reactive oxygen species (ROS) (4). Overproduction of ROS may cause oxidative damage to biomolecules and subsequently DNA damage, ultimately leading to the development of neurodegenerative diseases.…”

Changes in Vascular and Immune Cell Content of an LPS Treated Rat Olfactory Bulb PD Model, Measured by Fluorescence Deconvolution Microscopy

“…Many factors play a role in chronic neurodegeneration which leads to Parkinson's disease (PD), including inflammation [1], cytokine syntheses and release [1], protein recycling-ubiquitination problems [2], glial cell activation [3], loss of astrocyte support [4], neurotrophic factors [2], nitric oxide synthase [5] and mitochondrial dysfunction [2]. However, recent reports have shown that circulating cells [6] are also involved in disease progression, which coupled with vascular damage [7], points to both peripheral and innate factors and cell involvement in the ensuing demise of neurons.…”