title: 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.
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research/FDA, Bldg. 53D, HFT-32, Jefferson, AR 72079, USA. Sumit.Sarkar@fda.hhs.gov.
authors.forename: Sumit
authors.initials: S
authors.lastname: Sarkar
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research/FDA, Bldg. 53D, HFT-32, Jefferson, AR 72079, USA. James.Raymick@fda.hhs.gov.
authors.forename: James
authors.initials: J
authors.lastname: Raymick
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research/FDA, Bldg. 53D, HFT-32, Jefferson, AR 72079, USA. syed.imam@fda.hhs.gov.
authors.forename: Syed
authors.initials: S
authors.lastname: Imam
mesh_terms: D000818:Animals; D017209:Apoptosis; D015415:Biomarkers; D002986:Clinical Trials as Topic; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D010300:Parkinson Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D066263:Protein Aggregation, Pathological / Q000378:metabolism; D017510:Protein Folding; D017382:Reactive Oxygen Species / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species
keywords: ">l-DOPA; Parkinson’s disease; deep brain stimulation; dopamine; olfaction; striatum; substantia nigra