title: Changing paradigm to target microglia in neurodegenerative diseases: from anti-inflammatory strategy to active immunomodulation.
abstract: BACKGROUND
  The importance of microglia in most neurodegenerative pathologies, from Parkinson's disease to amyotrophic lateral sclerosis and Alzheimer's disease, is increasingly recognized. Until few years ago, microglial activation in pathological conditions was considered dangerous to neurons due to its causing inflammation. Today we know that these glial cells also play a crucial physiological and neuroprotective role, which is altered in neurodegenerative conditions.
  
  
  METHODS
  The neuroinflammatory hypothesis for neurodegenerative diseases has led to the trial of anti-inflammatory agents as therapeutics with largely disappointing results. New information about the physiopathological role of microglia has highlighted the importance of immunomodulation as a potential new therapeutic approach. This review summarizes knowledge on microglia as a potential therapeutic target in the most common neurodegenerative diseases, with focus on compounds directed toward the modulation of microglial immune response through specific molecular pathways.
  
  
  CONCLUSIONS
  Here we support the innovative concept of targeting microglial cells by modulating their activity, rather than simply trying to counteract their inflammatory neurotoxicity, as a potential therapeutic approach for neurodegenerative diseases. The advantage of this therapeutic approach could be to reduce neuroinflammation and toxicity, while at the same time strengthening intrinsic neuroprotective properties of microglia and promoting neuroregeneration.
authors.affiliation: a Department of Pharmacy and Biotechnology , University of Bologna , Bologna , Italy.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Peña-Altamira
authors.affiliation: a Department of Pharmacy and Biotechnology , University of Bologna , Bologna , Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Prati
authors.affiliation: a Department of Pharmacy and Biotechnology , University of Bologna , Bologna , Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Massenzio
authors.affiliation: a Department of Pharmacy and Biotechnology , University of Bologna , Bologna , Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Virgili
authors.affiliation: a Department of Pharmacy and Biotechnology , University of Bologna , Bologna , Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Contestabile
authors.affiliation: a Department of Pharmacy and Biotechnology , University of Bologna , Bologna , Italy.
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Bolognesi
authors.affiliation: a Department of Pharmacy and Biotechnology , University of Bologna , Bologna , Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Monti
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D006801:Humans; D056747:Immunomodulation; D017628:Microglia / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000628:therapy*
chemical_list: D000893:Anti-Inflammatory Agents
keywords: Drug targets; M2 and M1 phenotypes; immunomodulation; microglia; neurodegenerative diseases