title: Vaccination with heat-shocked mononuclear cells as a strategy for treating neurodegenerative disorders driven by microglial inflammation.
abstract: Naturally occurring T regulatory cells targeting epitopes derived from various heat shock proteins escape thymic negative selection and can be activated by vaccination with heat shock proteins; hence, vaccination with such proteins has exerted favorable effects on rodent models of autoimmune disorders. A more elegant way to achieve such vaccination, first evaluated clinically by Al-Harbi in the early 1990s, is to subject mononuclear cells to survivable heat shock ex vivo, incubate them at physiological temperature for a further 24-48 h, and then inject them subcutaneously; anecdotally, beneficial effects were observed with this strategy in a wide range of autoimmune and inflammatory conditions. There is growing evidence that M1-activated microglia play a primary or secondary role in the pathogenesis of numerous neurodegenerative diseases, as well as in major depression. T regulatory cells, by polarizing microglial toward a reparative M2 phenotype, have the potential to aid control of such disorders. It would be appropriate to test the heat-shocked mononuclear cell vaccination strategy in animal models of neurodegeneration and major depression, and to evaluate this approach clinically if such studies yield encouraging results.
authors: Catalytic Longevity, 7831 Rush Rose Drive, Apt. 316, Carlsbad, California 92009, United States. Electronic address: markfmccarty@gmail.com.
authors: Mark F
authors: MF
authors: McCarty
authors: Saleh A
authors: SA
authors: Al-Harbi
mesh_terms: D018869:Heat-Shock Response / Q000502:physiology*; D006801:Humans; D017628:Microglia / Q000473:pathology*; D018448:Models, Immunological; D019636:Neurodegenerative Diseases / Q000473:pathology* / Q000628:therapy*; D052980:Phycobilins; D010798:Phycocyanin; D050378:T-Lymphocytes, Regulatory / Q000502:physiology / Q000637:transplantation*; D014611:Vaccination / Q000379:methods*
chemical_list: D052980:Phycobilins; D010798:Phycocyanin; C011069:phycocyanobilin