title: Parkinson's Disease, Diabetes and Cognitive Impairment.
abstract: BACKGROUND
  Parkinson's disease is a chronic neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons. The pathophysiological mechanisms underlying Parkinson's are still unknown. Mitochondrial dysfunction, abnormal protein aggregation, increased neuroinflammation and impairment of brain glucose metabolism are shared processes among insulinresistance, diabetes and neurodegeneration and have been suggested as key mechanisms in development of Parkinson's and cognitive impairment.
  
  
  OBJECTIVE
  To review experimental and clinical evidence of underlying Parkinson's pathophysiology in common with diabetes and cognitive impairment. Anti-diabetic agents and recent patents for insulin-resistance that might be repositioned in the treatment of Parkinson's also have been included in this review.
  
  
  METHODS
  A narrative review using MEDLINE database.
  
  
  RESULTS
  Common antidiabetic treatments such as DPP4 inhibitors, GLP-1 agonists and metformin have shown promise in the treatment of Parkinson's disease and cognitive impairment in animals and humans. Study of the pathophysiology of neurodegeneration common between diabetes and Parkinson's disease has given rise to new treatment possibilities. Patents published in the last 5 years could be used in novel approaches to Parkinson's treatment by targeting specific pathophysiology proteins, such as Nurr1, PINK1 and NrF2, while patents to improve penetration of the blood brain barrier could allow improved efficacy of existing treatments.
  
  
  CONCLUSIONS
  Further studies using GLP-1 agonists and DPP-4 inhibitors to treat PD are warranted as they have shown promise.
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Ashraghi
authors.forename: Gennaro
authors.initials: G
authors.lastname: Pagano
authors.forename: Sotirios
authors.initials: S
authors.lastname: Polychronis
authors.forename: Flavia
authors.initials: F
authors.lastname: Niccolini
authors.affiliation: Neurodegeneration Imaging Group, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), 125 Coldharbour Lane, Camberwell, London, SE5 9NU; UK. marios.politis@kcl.ac.uk.
authors.forename: Marios
authors.initials: M
authors.lastname: Politis
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use; D055808:Drug Discovery; D058492:Drug Repositioning; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D054795:Incretins / Q000627:therapeutic use; D007333:Insulin Resistance; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D010330:Patents as Topic
chemical_list: D000978:Antiparkinson Agents; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D054795:Incretins; D018696:Neuroprotective Agents