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Neuroprotective and Therapeutic Strategies against Parkinson's Disease: Recent Perspectives.
Int J Mol Sci. 2016 Jun 08; 17(6)IJ

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.

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Authors+Show Affiliations

Sarkar S
Division of Neurotoxicology, National Center for Toxicological Research/FDA, Bldg. 53D, HFT-32, Jefferson, AR 72079, USA. Sumit.Sarkar@fda.hhs.gov.
Raymick J
Division of Neurotoxicology, National Center for Toxicological Research/FDA, Bldg. 53D, HFT-32, Jefferson, AR 72079, USA. James.Raymick@fda.hhs.gov.
Imam S
Division of Neurotoxicology, National Center for Toxicological Research/FDA, Bldg. 53D, HFT-32, Jefferson, AR 72079, USA. syed.imam@fda.hhs.gov.

MeSH

AnimalsApoptosisBiomarkersClinical Trials as TopicCorpus StriatumDopaminergic NeuronsHumansMitochondriaMolecular Targeted TherapyNerve Growth FactorsNeuroprotective AgentsOxidative StressParkinson DiseaseProtein Aggregation, PathologicalProtein FoldingReactive Oxygen SpeciesTreatment Outcome

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

27338353

Citation

Sarkar, Sumit, et al. "Neuroprotective and Therapeutic Strategies Against Parkinson's Disease: Recent Perspectives." International Journal of Molecular Sciences, vol. 17, no. 6, 2016.
Sarkar S, Raymick J, Imam S. Neuroprotective and Therapeutic Strategies against Parkinson's Disease: Recent Perspectives. Int J Mol Sci. 2016;17(6).
Sarkar, S., Raymick, J., & Imam, S. (2016). Neuroprotective and Therapeutic Strategies against Parkinson's Disease: Recent Perspectives. International Journal of Molecular Sciences, 17(6). https://doi.org/10.3390/ijms17060904
Sarkar S, Raymick J, Imam S. Neuroprotective and Therapeutic Strategies Against Parkinson's Disease: Recent Perspectives. Int J Mol Sci. 2016 Jun 8;17(6) PubMed PMID: 27338353.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuroprotective and Therapeutic Strategies against Parkinson's Disease: Recent Perspectives. AU - Sarkar,Sumit, AU - Raymick,James, AU - Imam,Syed, Y1 - 2016/06/08/ PY - 2016/04/25/received PY - 2016/05/27/revised PY - 2016/05/30/accepted PY - 2016/6/25/entrez PY - 2016/6/25/pubmed PY - 2017/4/7/medline KW - ">l-DOPA KW - Parkinson’s disease KW - deep brain stimulation KW - dopamine KW - olfaction KW - striatum KW - substantia nigra JF - International journal of molecular sciences JO - Int J Mol Sci VL - 17 IS - 6 N2 - 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. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/27338353/Neuroprotective_and_Therapeutic_Strategies_against_Parkinson's_Disease:_Recent_Perspectives_ DB - PRIME DP - Unbound Medicine ER -