Neuroprotection by immunomodulatory agents in animal models of Parkinson’s disease

Journal Article · Fri Aug 17 00:00:00 EDT 2018 · Neural Regeneration Research

DOI:https://doi.org/10.4103/1673-5374.237108· OSTI ID:1628698

Martinez, Bridget ^[1]; Peplow, Philip V. ^[2]

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1. Univ. of California, Merced, CA (United States). Dept. of Molecular & Cellular Biology; St. Georges Univ. (Grenada). School of Medicine, Dept. of Medicine; Los Alamos National Lab. (LANL), Los Alamos, NM (United States); DOE/OSTI
2. Univ. of Otago, Dunedin (New Zealand). Dept. of Anatomy

Parkinson’s disease (PD) is an age-related neurodegenerative disease for which the characteristic motor symptoms emerge after an extensive loss of dopamine containing neurons. The cell bodies of these neurons are present in the substantia nigra, with the nerve terminals being in the striatum. Both innate and adaptive immune responses may contribute to dopaminergic neurodegeneration and disease progression is potentially linked to these. Studies in the last twenty years have indicated an important role for neuroinflammation in PD through degeneration of the nigrostriatal dopaminergic pathway. Characteristic of neuroinflammation is the activation of brain glial cells, principally microglia and astrocytes that release various soluble factors. Many of these factors are proinflammatory and neurotoxic and harmful to nigral dopaminergic neurons. Recent studies have identified several different agents with immunomodulatory properties that protected dopaminergic neurons from degeneration and death in animal models of PD. All of the agents were effective in reducing the motor deficit and alleviating dopaminergic neurotoxicity and, when measured, preventing the decrease of dopamine upon being administered therapeutically after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 6-hydroxydopamine, rotenone-lesioning or delivery of adeno-associated virus-α-synuclein to the ventral midbrain of animals. Some of these agents were shown to exert an anti-inflammatory action, decrease oxidative stress, and reduce lipid peroxidation products. Activation of microglia and astrocytes was also decreased, as well as infiltration of T cells into the substantia nigra. Pretreatment with fingolimod, tanshinoine I, dimethyl fumarate, thalidomide, or cocaine- and amphetamine-regulated transcript peptide as a preventive strategy ameliorated motor deficits and nigral dopaminergic neurotoxicity in brain-lesioned animals. We conclude immunomodulatory agents could be used to treat patients with early clinical signs of the disease or potentially even prior to disease onset in those identified as having pre-disposing risk, including genetic factors.

• Research Organization: Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
• Sponsoring Organization: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
• Grant/Contract Number: AC52-06NA25396
• OSTI ID: 1628698
• Journal Information: Neural Regeneration Research, Journal Name: Neural Regeneration Research Journal Issue: 9 Vol. 13; ISSN 1673-5374
• Publisher: Chinese Association of Rehabilitation Medicine (CARM)
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
Parkinson’s disease
animal models
astrogliosis
cell biology
immunomodulatory agents
inflammation
microgliosis
neuroprotection
neurosciences & neurology
oxidative stress