Seite - 52 - in Advances in Neuroimmunology

brain sciences Review ImmunomodulatorsasTherapeuticAgents in MitigatingtheProgressionofParkinson’sDisease BethanyGrimmig1, JoshMorganti 2,KevinNash3 andPaulaCBickford1,4,* 1 CenterofExcellence forAgingandBrainRepair,DepartmentofNeurosurgeryandBrainRepair, MorsaniCollegeofMedicine,UniversityofSouthFlorida,Tampa,FL33612,USA; bgrimmig@health.usf.edu 2 Sanders-BrownCenteronAging,DepartmentofAnatomyandNeurobiology,UniversityofKentucky, Lexington,KY40508,USA; josh.morganti@uky.edu 3 ByrdAlzheimer’s Institute,DepartmentofMolecularPharmacologyandPhysiology, MorsaniCollegeofMedicine,UniversityofSouthFlorida,Tampa,FL33613,USA;Knash@health.usf.edu 4 JamesAHaleyVAHospital, 13000BruceBDownsBlvd,Tampa,FL33612,USA * Correspondence: pbickfor@health.usf.edu;Tel.:+1-813-974-3238 AcademicEditor:DonnaGruol Received: 9 July2016;Accepted: 20September2016;Published: 23September2016 Abstract:Parkinson’sdisease (PD) isacommonneurodegenerativedisorder thatprimarilyafflicts theelderly. It is characterizedbymotordysfunctionduetoextensiveneuronloss in thesubstantia nigraparscompacta. Therearemultiplebiologicalprocesses thatarenegatively impactedduringthe pathogenesisofPD,andareimplicatedinthecelldeathinthisregion.Neuroinflammationisevidently involvedinPDpathologyandmitigatingthe inflammatorycascadehasbeenatherapeutic strategy. Ageis thenumberonerisk factor forPDandthusneedstobeconsideredinthecontextofdisease pathology.Here,wediscuss theroleofneuroinflammationwithin thecontextofagingas itapplies to thedevelopment of PD, and thepotential for two representative compounds, fractalkine and astaxanthin, to attenuate the pathophysiology thatmodulates neurodegeneration that occurs in Parkinson’sdisease. Keywords:Parkinson’sdisease;neuroinflammation;microglia; fractalkine;astaxanthin 1. Parkinson’sDisease Parkinson’s disease (PD) is adebilitating condition that affectsmillions of peopleworldwide. With the development of drugs to treat complications associated with significant morbidity and mortality,patientsare livingupto20yearsafter thediagnosisofPD.Althoughtheuseofmedications has led to a relative improvement in quality of life, thesepatients are often substantially disabled, requiringsignificanthealth careandcompensation for lossofwages. It hasbeenprojected that the prevalenceofPDwilldoubleby2040, indicatingsevereeconomicconsequencestocomeastheincidence increases. Therearecurrentlynoavailablemedications thatpreventorreverse theneurodegeneration thatcauses thesedisabilities [1]. Parkinson’s disease is primarily characterizedneuroanatomically by thedegeneration of the neurons in the substantia nigra pars compacta (SN), resulting in a substantial loss of dopamine (DA)afferents to thestriatumandsubsequentmotor impairment. It isestimatedthatnearly50%of dopaminergic cells in the SN have been lost prior to clinical presentation of motor dysfunction. It is now understood that PD pathology extends to extra nigral regions including the locus coeruleus,nucleusbasalisofMeynert,peduculopontinenucleus, intralaminar thalamus,andlateral hypothalamus suggestingdysfunctionandneurodegeneration inmanyareasof thebrain [2]. It is histopathologicallycharacterizedbythe formationofLewybodies, intraneuronalprotein inclusions BrainSci. 2016,6, 41 52 www.mdpi.com/journal/brainsci