Display options
Cite
Castillo X, Castro-Obregón S, Gutiérrez-Becker B, et al. Re-thinking the Etiological Framework of Neurodegeneration. Front Neurosci. 2019;13:728doi: 10.3389/fnins.2019.00728.
Castillo, X., Castro-Obregón, S., Gutiérrez-Becker, B., Gutiérrez-Ospina, G., Karalis, N., Khalil, A. A., Lopez-Noguerola, J. S., Rodríguez, L. L., Martínez-Martínez, E., Perez-Cruz, C., Pérez-Velázquez, J., Piña, A. L., Rubio, K., García, H. P. S., Syeda, T., Vanoye-Carlo, A., Villringer, A., Winek, K., & Zille, M. (2019). Re-thinking the Etiological Framework of Neurodegeneration. Frontiers in neuroscience, 13728. https://doi.org/10.3389/fnins.2019.00728
Castillo, Ximena, et al. "Re-thinking the Etiological Framework of Neurodegeneration." Frontiers in neuroscience vol. 13 (2019): 728. doi: https://doi.org/10.3389/fnins.2019.00728
Castillo X, Castro-Obregón S, Gutiérrez-Becker B, Gutiérrez-Ospina G, Karalis N, Khalil AA, Lopez-Noguerola JS, Rodríguez LL, Martínez-Martínez E, Perez-Cruz C, Pérez-Velázquez J, Piña AL, Rubio K, García HPS, Syeda T, Vanoye-Carlo A, Villringer A, Winek K, Zille M. Re-thinking the Etiological Framework of Neurodegeneration. Front Neurosci. 2019 Jul 24;13:728. doi: 10.3389/fnins.2019.00728. eCollection 2019. PMID: 31396030; PMCID: PMC6667555.
Copy Download .nbib Format: NLM
Share it on

Front Neurosci. 2019 Jul 24;13:728. doi: 10.3389/fnins.2019.00728. eCollection 2019.

Re-thinking the Etiological Framework of Neurodegeneration.

Frontiers in neuroscience

Ximena Castillo, Susana Castro-Obregón, Benjamin Gutiérrez-Becker, Gabriel Gutiérrez-Ospina, Nikolaos Karalis, Ahmed A Khalil, José Sócrates Lopez-Noguerola, Liliana Lozano Rodríguez, Eduardo Martínez-Martínez, Claudia Perez-Cruz, Judith Pérez-Velázquez, Ana Luisa Piña, Karla Rubio, Héctor Pedro Salazar García, Tauqeerunnisa Syeda, America Vanoye-Carlo, Arno Villringer, Katarzyna Winek, Marietta Zille

Affiliations

  1. Instituto de Neurobiología, Universidad Nacional Autónoma de México, Mexico City, Mexico.
  2. Institute of Neurobiology, University of Puerto Rico, San Juan, PR, United States.
  3. Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico.
  4. Artificial Intelligence in Medical Imaging KJP, Ludwig Maximilian University of Munich, Munich, Germany.
  5. Laboratorio de Biología de Sistemas, Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas y Coordinación de Psicobiología y Neurociencias, Facultad de Psicología, Universidad Nacional Autónoma de México, Mexico City, Mexico.
  6. Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
  7. Center for Stroke Research Berlin, Charité-Universitätsmedizin Berlin, Berlin, Germany.
  8. Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany.
  9. Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
  10. School of Health Sciences, Department of Gerontology, Autonomous University of Hidalgo State, Pachuca, Mexico.
  11. Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico.
  12. Cell Communication & Extracellular Vesicles Laboratory, Instituto Nacional de Medicina Genómica, Mexico City, Mexico.
  13. National Polytechnic Institute, Center of Research in Advanced Studies, Mexico City, Mexico.
  14. Departamento de Matemáticas y Mecánica, Instituto de Investigaciones en Matemáticas Aplicadas y Sistemas, Universidad Nacional Autónoma de México, Mexico City, Mexico.
  15. Mathematische Modellierung Biologischer Systeme, Fakultät für Mathematik, Technische Universität München, Munich, Germany.
  16. Department of Neurosurgery, Charité-Universitätsmedizin Berlin, Berlin, Germany.
  17. Lung Cancer Epigenetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
  18. Leibniz-Forschungsinstitut für Molekulare Pharmakologie, Berlin, Germany.
  19. Laboratorio de Neurociencias, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City, Mexico.
  20. The Shimon Peres Postdoctoral Fellow at the Edmond and Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
  21. Department of Experimental Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
  22. Institute for Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany.
  23. Institute for Medical and Marine Biotechnology, University of Lübeck, Lübeck, Germany.
  24. Fraunhofer Research Institution for Marine Biotechnology and Cell Technology, Lübeck, Germany.

PMID: 31396030 PMCID: PMC6667555 DOI: 10.3389/fnins.2019.00728

Abstract

Neurodegenerative diseases are among the leading causes of disability and death worldwide. The disease-related socioeconomic burden is expected to increase with the steadily increasing life expectancy. In spite of decades of clinical and basic research, most strategies designed to manage degenerative brain diseases are palliative. This is not surprising as neurodegeneration progresses "silently" for decades before symptoms are noticed. Importantly, conceptual models with heuristic value used to study neurodegeneration have been constructed retrospectively, based on signs and symptoms already present in affected patients; a circumstance that may confound causes and consequences. Hence, innovative, paradigm-shifting views of the etiology of these diseases are necessary to enable their timely prevention and treatment. Here, we outline four alternative views, not mutually exclusive, on different etiological paths toward neurodegeneration. First, we propose neurodegeneration as being a secondary outcome of a primary cardiovascular cause with vascular pathology disrupting the vital homeostatic interactions between the vasculature and the brain, resulting in cognitive impairment, dementia, and cerebrovascular events such as stroke. Second, we suggest that the persistence of senescent cells in neuronal circuits may favor, together with systemic metabolic diseases, neurodegeneration to occur. Third, we argue that neurodegeneration may start in response to altered body and brain trophic interactions established via the hardwire that connects peripheral targets with central neuronal structures or by means of extracellular vesicle (EV)-mediated communication. Lastly, we elaborate on how lifespan body dysbiosis may be linked to the origin of neurodegeneration. We highlight the existence of bacterial products that modulate the gut-brain axis causing neuroinflammation and neuronal dysfunction. As a concluding section, we end by recommending research avenues to investigate these etiological paths in the future. We think that this requires an integrated, interdisciplinary conceptual research approach based on the investigation of the multimodal aspects of physiology and pathophysiology. It involves utilizing proper conceptual models, experimental animal units, and identifying currently unused opportunities derived from human data. Overall, the proposed etiological paths and experimental recommendations will be important guidelines for future cross-discipline research to overcome the translational roadblock and to develop causative treatments for neurodegenerative diseases.

Keywords: body–brain trophism; dysbiosis; lifespan; senescence; vascular pathology

References

  1. Acta Neurol Scand. 1999 Jul;100(1):34-41 - PubMed
  2. Neurology. 1999 Oct 22;53(7):1391-6 - PubMed
  3. Exp Neurol. 1999 Dec;160(2):515-22 - PubMed
  4. Ann N Y Acad Sci. 1999;893:154-75 - PubMed
  5. Neurobiol Aging. 2000 Jan-Feb;21(1):49-55 - PubMed
  6. N Engl J Med. 2000 Aug 17;343(7):450-6 - PubMed
  7. Eur J Neurosci. 2000 Aug;12(8):3073-7 - PubMed
  8. Nature. 2000 Sep 14;407(6801):233-41 - PubMed
  9. J Neurol Neurosurg Psychiatry. 2001 Jan;70(1):9-14 - PubMed
  10. Brain Res. 2000 Dec 1;885(1):1-5 - PubMed
  11. Neurology. 2001 Jan 9;56(1):42-8 - PubMed
  12. J Hypertens. 2001 Sep;19(9):1515-21 - PubMed
  13. Nature. 2002 Apr 4;416(6880):535-9 - PubMed
  14. Acta Neuropathol. 2002 May;103(5):481-7 - PubMed
  15. Neurobiol Aging. 2003 Mar-Apr;24(2):197-211 - PubMed
  16. J Clin Invest. 2003 Jan;111(1):3-10 - PubMed
  17. Bull World Health Organ. 2002;80(12):983-4 - PubMed
  18. J Neural Transm (Vienna). 2003 May;110(5):517-36 - PubMed
  19. Nat Rev Neurosci. 2004 May;5(5):347-60 - PubMed
  20. Hum Mol Genet. 2004 Jun 1;13(11):1183-92 - PubMed
  21. Neurobiol Aging. 2004 Jul;25(6):783-93 - PubMed
  22. Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9683-8 - PubMed
  23. Metab Brain Dis. 2004 Dec;19(3-4):151-67 - PubMed
  24. Neurology. 2005 Apr 26;64(8):1358-65 - PubMed
  25. Ann Neurol. 2005 Jun;57(6):789-94 - PubMed
  26. Mov Disord. 2005 Oct;20(10):1350-3 - PubMed
  27. Environ Health Perspect. 2005 Sep;113(9):1250-6 - PubMed
  28. Lancet. 2005 Oct 1;366(9492):1197-209 - PubMed
  29. J Appl Physiol (1985). 2006 Jan;100(1):328-35 - PubMed
  30. Br J Pharmacol. 2006 Jan;147 Suppl 1:S232-40 - PubMed
  31. Appl Environ Microbiol. 2006 Feb;72(2):1027-33 - PubMed
  32. Stroke. 2006 Apr;37(4):1010-5 - PubMed
  33. J Clin Gastroenterol. 2006 Mar;40(3):235-43 - PubMed
  34. J Physiol. 2006 Jul 1;574(Pt 1):7-15 - PubMed
  35. J Neural Transm (Vienna). 2006 Sep;113(9):1169-76 - PubMed
  36. Neuroscience. 2006 Sep 29;142(1):267-83 - PubMed
  37. Brain. 2006 Nov;129(Pt 11):2957-65 - PubMed
  38. J Physiol. 1890 Jan;11(1-2):85-158.17 - PubMed
  39. Brain. 2006 Nov;129(Pt 11):2908-22 - PubMed
  40. Ann Neurol. 2007 May;61(5):403-10 - PubMed
  41. Cogn Behav Neurol. 2007 Jun;20(2):93-8 - PubMed
  42. Ann Neurol. 1991 Nov;30(5):686-93 - PubMed
  43. Curr Neurovasc Res. 2007 Aug;4(3):216-27 - PubMed
  44. Science. 1989 May 26;244(4907):993 - PubMed
  45. Neurobiol Aging. 2009 Mar;30(3):337-52 - PubMed
  46. Nat Rev Neurosci. 2007 Oct;8(10):766-75 - PubMed
  47. J Neurophysiol. 2008 May;99(5):2035-47 - PubMed
  48. Neuroscience. 2007 Nov 23;149(4):739-46 - PubMed
  49. Arch Neurol. 2007 Dec;64(12):1734-40 - PubMed
  50. Gerontology. 2008;54(1):6-17 - PubMed
  51. Neuron. 2008 Jan 24;57(2):178-201 - PubMed
  52. Br J Radiol. 2007 Dec;80 Spec No 2:S128-45 - PubMed
  53. Acta Neuropathol. 2008 Aug;116(2):169-82 - PubMed
  54. J Clin Pathol. 2008 Jun;61(6):697-706 - PubMed
  55. Brain. 2008 Jul;131(Pt 7):1903-11 - PubMed
  56. Annu Rev Neurosci. 2008;31:247-69 - PubMed
  57. J Neuroinflammation. 2008 Aug 29;5:37 - PubMed
  58. Hypertension. 2008 Dec;52(6):1120-6 - PubMed
  59. Eur Radiol. 2009 Apr;19(4):1011-8 - PubMed
  60. Biochim Biophys Acta. 2009 May;1792(5):395-400 - PubMed
  61. Cancer Res. 1991 May 15;51(10):2531-5 - PubMed
  62. Neurotoxicology. 2009 Jan;30(1):136-43 - PubMed
  63. Biochim Biophys Acta. 2009 May;1792(5):432-43 - PubMed
  64. J Neurol. 2009 May;256(5):758-67 - PubMed
  65. Arch Neurol. 2009 Mar;66(3):343-8 - PubMed
  66. Cerebrovasc Dis. 2009;27 Suppl 1:25-37 - PubMed
  67. Neurology. 2009 May 5;72(18):1614-6 - PubMed
  68. J Alzheimers Dis. 2009;18(3):713-25 - PubMed
  69. Lancet. 1990 Mar 31;335(8692):765-74 - PubMed
  70. Eur J Neurosci. 2009 Sep;30(5):735-41 - PubMed
  71. Neurology. 2009 Sep 1;73(9):674-80 - PubMed
  72. Acta Neuropathol. 1990;79(6):581-3 - PubMed
  73. Neurology. 2009 Sep 8;73(10):768-74 - PubMed
  74. J Neuroimmunol. 2009 Nov 30;216(1-2):39-50 - PubMed
  75. Cell. 2009 Oct 16;139(2):393-404 - PubMed
  76. Clin Nutr. 2010 Jun;29(3):365-9 - PubMed
  77. Ageing Res Rev. 2011 Jan;10(1):71-9 - PubMed
  78. Annu Rev Pathol. 2010;5:99-118 - PubMed
  79. Neurodegener Dis. 2010;7(1-3):112-5 - PubMed
  80. Acta Neuropathol. 2010 Jun;119(6):689-702 - PubMed
  81. PLoS Med. 2010 Mar 30;7(3):e1000245 - PubMed
  82. J Neurochem. 2010 Jun;113(6):1577-88 - PubMed
  83. Am J Pathol. 2010 Jul;177(1):300-10 - PubMed
  84. Acta Neuropathol. 2010 Jul;120(1):1-12 - PubMed
  85. J Neurochem. 2010 Sep;114(6):1687-700 - PubMed
  86. Curr Neurovasc Res. 2010 Aug;7(3):251-67 - PubMed
  87. PLoS Biol. 2010 Jun 29;8(6):e1000412 - PubMed
  88. Biochim Biophys Acta. 2011 Feb;1812(2):252-64 - PubMed
  89. J Alzheimers Dis. 2010;21(3):813-22 - PubMed
  90. Ann Neurol. 2010 Aug;68(2):231-40 - PubMed
  91. Stroke. 2010 Oct;41(10):2348-52 - PubMed
  92. Soc Psychiatry Psychiatr Epidemiol. 2011 Nov;46(11):1173-9 - PubMed
  93. J Neurol Neurosurg Psychiatry. 2011 Feb;82(2):126-35 - PubMed
  94. Nat Med. 2010 Nov;16(11):1210-4 - PubMed
  95. Nutr Rev. 2010 Dec;68 Suppl 2:S74-87 - PubMed
  96. Mol Cell Neurosci. 2011 Feb;46(2):409-18 - PubMed
  97. Curr Opin Neurol. 2011 Feb;24(1):69-74 - PubMed
  98. Eur Neurol. 2011;65(1):23-31 - PubMed
  99. Comp Med. 2010 Oct;60(5):336-47 - PubMed
  100. Ann Neurol. 2011 Jan;69(1):13-21 - PubMed
  101. Nat Rev Neurol. 2011 Apr;7(4):229-36 - PubMed
  102. J Neurol Sci. 2011 Jun 15;305(1-2):22-7 - PubMed
  103. J Alzheimers Dis. 2011;26(1):187-97 - PubMed
  104. Eur J Neurosci. 2011 Jul;34(1):3-11 - PubMed
  105. Clin Ther. 2011 May;33(5):511-27 - PubMed
  106. Trends Microbiol. 2011 Jul;19(7):349-59 - PubMed
  107. Case Rep Neurol. 2011 May;3(2):136-40 - PubMed
  108. Stroke. 2011 Sep;42(9):2595-604 - PubMed
  109. Stroke. 2011 Sep;42(9):2672-713 - PubMed
  110. Cardiol Res Pract. 2011;2011:156146 - PubMed
  111. Nature. 2011 Aug 31;477(7362):90-4 - PubMed
  112. Eur Heart J. 2012 Apr;33(7):829-37, 837a-837d - PubMed
  113. PLoS One. 2011;6(12):e28032 - PubMed
  114. Neurobiol Aging. 2012 Oct;33(10):2324-33 - PubMed
  115. Diabetes. 2012 May;61(5):1234-42 - PubMed
  116. J Biol Chem. 2012 May 11;287(20):16820-34 - PubMed
  117. J Aging Res. 2012;2012:384017 - PubMed
  118. J Neuroinflammation. 2012 Apr 24;9:74 - PubMed
  119. Dig Dis Sci. 2012 Aug;57(8):2096-102 - PubMed
  120. Mol Neurobiol. 2013 Apr;47(2):561-74 - PubMed
  121. Gut Microbes. 2012 Jul-Aug;3(4):279-88 - PubMed
  122. Stroke. 2012 Oct;43(10):2637-42 - PubMed
  123. PLoS One. 2012;7(9):e45069 - PubMed
  124. Stroke. 2012 Dec;43(12):3319-24 - PubMed
  125. Dis Model Mech. 2012 Nov;5(6):718-25 - PubMed
  126. Nat Commun. 2012;3:1245 - PubMed
  127. ISRN Pediatr. 2012;2012:975685 - PubMed
  128. Lancet. 2012 Dec 15;380(9859):2224-60 - PubMed
  129. Orphanet J Rare Dis. 2013 Jan 10;8:6 - PubMed
  130. Biochim Biophys Acta. 2013 Apr;1832(4):527-41 - PubMed
  131. J Neurol Neurosurg Psychiatry. 2013 Jun;84(6):624-9 - PubMed
  132. Neuron. 2013 Mar 20;77(6):1039-46 - PubMed
  133. Neurology. 2013 Apr 23;80(17):1551-6 - PubMed
  134. N Engl J Med. 2013 Apr 25;368(17):1575-84 - PubMed
  135. Nat Rev Gastroenterol Hepatol. 2013 Jun;10(6):326-7 - PubMed
  136. J Lipid Res. 2013 Sep;54(9):2325-40 - PubMed
  137. Brain. 2013 Sep;136(Pt 9):2697-706 - PubMed
  138. Lancet Neurol. 2013 Aug;12(8):822-38 - PubMed
  139. J Gerontol A Biol Sci Med Sci. 2013 Sep;68(9):1045-56 - PubMed
  140. Trends Neurosci. 2013 Nov;36(11):674-84 - PubMed
  141. Exp Neurol. 2013 Nov;249:120-31 - PubMed
  142. Glia. 2013 Nov;61(11):1795-806 - PubMed
  143. Biogerontology. 2013 Dec;14(6):651-62 - PubMed
  144. Front Cell Neurosci. 2013 Sep 17;7:153 - PubMed
  145. Front Neurosci. 2013 Oct 07;7:177 - PubMed
  146. J Alzheimers Dis. 2014;39(1):169-79 - PubMed
  147. Nat Rev Neurol. 2013 Dec;9(12):687-97 - PubMed
  148. Neuron. 2013 Nov 20;80(4):844-66 - PubMed
  149. Neurology. 2014 Jan 7;82(1):57-62 - PubMed
  150. Methods Mol Biol. 2014;1135:3-20 - PubMed
  151. JAMA Psychiatry. 2014 Apr;71(4):412-22 - PubMed
  152. Circ Res. 2014 Apr 25;114(9):1453-68 - PubMed
  153. Nature. 2014 May 22;509(7501):439-46 - PubMed
  154. PLoS Biol. 2014 Jun 03;12(6):e1001874 - PubMed
  155. Nat Rev Mol Cell Biol. 2014 Jul;15(7):482-96 - PubMed
  156. J Alzheimers Dis. 2015;43(2):415-24 - PubMed
  157. PLoS Comput Biol. 2014 Aug 28;10(8):e1003728 - PubMed
  158. Parkinsonism Relat Disord. 2014 Nov;20(11):1260-2 - PubMed
  159. J Alzheimers Dis. 2015;43(3):957-66 - PubMed
  160. J Genet Genomics. 2014 Sep 20;41(9):485-95 - PubMed
  161. Exp Gerontol. 2015 Aug;68:3-7 - PubMed
  162. Nature. 1989 Sep 21;341(6239):226-30 - PubMed
  163. J Biol Chem. 2015 Jan 30;290(5):2969-82 - PubMed
  164. Gerontology. 2015;61(4):327-35 - PubMed
  165. Front Aging Neurosci. 2014 Dec 05;6:304 - PubMed
  166. Microb Ecol Health Dis. 2015 Feb 02;26:26191 - PubMed
  167. Front Aging Neurosci. 2015 Feb 10;7:9 - PubMed
  168. Neuroscience. 2015 Nov 19;309:173-90 - PubMed
  169. Neurochem Res. 2015 Dec;40(12):2583-99 - PubMed
  170. J Alzheimers Dis Parkinsonism. 2015 Mar;5(1):177 - PubMed
  171. Nat Rev Gastroenterol Hepatol. 2015 Sep;12(9):497-506 - PubMed
  172. Auton Neurosci. 2015 Dec;193:1-6 - PubMed
  173. Mov Disord. 2015 Sep;30(10):1413-7 - PubMed
  174. J Comp Neurol. 2016 Apr 15;524(6):1236-58 - PubMed
  175. Parkinsonism Relat Disord. 2016 Jan;22 Suppl 1:S119-22 - PubMed
  176. JAMA Neurol. 2015 Nov;72(11):1288-94 - PubMed
  177. EBioMedicine. 2015 Jul 10;2(8):968-84 - PubMed
  178. Nat Neurosci. 2015 Nov;18(11):1584-93 - PubMed
  179. Nat Rev Neurosci. 2015 Nov;16(11):672-84 - PubMed
  180. Biomed Res Int. 2015;2015:412946 - PubMed
  181. J Am Heart Assoc. 2015 Nov 23;4(11):null - PubMed
  182. Curr Opin HIV AIDS. 2016 Mar;11(2):182-90 - PubMed
  183. Biochim Biophys Acta. 2016 May;1862(5):887-900 - PubMed
  184. PLoS Biol. 2016 Jan 04;14(1):e1002331 - PubMed
  185. Stroke. 2016 Mar;47(3):895-900 - PubMed
  186. Neuroscience. 2016 Apr 21;320:129-39 - PubMed
  187. Stem Cells Int. 2016;2016:6484713 - PubMed
  188. Acta Neuropathol. 1989;79(2):117-28 - PubMed
  189. Stroke. 2016 Apr;47(4):1068-77 - PubMed
  190. Brain. 2016 Mar;139(Pt 3):653-61 - PubMed
  191. Front Microbiol. 2016 Feb 17;7:185 - PubMed
  192. Mov Disord. 2016 Jun;31(6):782-90 - PubMed
  193. J Alzheimers Dis. 2016;51(4):979-84 - PubMed
  194. Nat Med. 2016 May;22(5):516-23 - PubMed
  195. J Biol Chem. 2016 Jun 10;291(24):12445-66 - PubMed
  196. Stroke. 2016 May;47(5):1354-63 - PubMed
  197. Brain Behav Immun. 2016 Oct;57:10-20 - PubMed
  198. Lancet Neurol. 2016 Jun;15(7):673-684 - PubMed
  199. FEMS Microbiol Rev. 2016 Jul;40(4):480-93 - PubMed
  200. Cell Death Differ. 2016 Sep 1;23(9):1515-28 - PubMed
  201. Science. 2016 Apr 29;352(6285):539-44 - PubMed
  202. Mol Biosyst. 2016 Jul 19;12(8):2562-71 - PubMed
  203. Lipids Health Dis. 2016 Jun 18;15:108 - PubMed
  204. Sci Rep. 2016 Jun 23;6:28635 - PubMed
  205. Mol Nutr Food Res. 2017 Jan;61(1): - PubMed
  206. Nature. 2016 Jul 06;535(7610):85-93 - PubMed
  207. J Neurosci. 2016 Jul 13;36(28):7428-40 - PubMed
  208. Nat Rev Gastroenterol Hepatol. 2016 Sep;13(9):517-28 - PubMed
  209. Sci Rep. 2016 Jul 21;6:30028 - PubMed
  210. Gut Microbes. 2016 Sep 2;7(5):365-83 - PubMed
  211. PLoS Biol. 2016 Aug 19;14(8):e1002533 - PubMed
  212. Alzheimers Dement. 2016 Apr;12(4):459-509 - PubMed
  213. EMBO Mol Med. 2016 Oct 4;8(10):1162-1183 - PubMed
  214. Front Aging Neurosci. 2016 Aug 31;8:208 - PubMed
  215. Nat Med. 2016 Nov;22(11):1277-1284 - PubMed
  216. Curr Alzheimer Res. 2017;14(4):426-440 - PubMed
  217. Neurobiol Aging. 2017 Jan;49:60-68 - PubMed
  218. Neurology. 2016 Nov 29;87(22):2324-2332 - PubMed
  219. J Neurosci. 2016 Dec 14;36(50):12624-12639 - PubMed
  220. J Biol Chem. 2016 Dec 23;291(52):26589-26597 - PubMed
  221. Development. 2017 Jan 1;144(1):106-114 - PubMed
  222. J Alzheimers Dis. 2017;56(1):385-390 - PubMed
  223. Neurobiol Dis. 2018 Jan;109(Pt B):226-248 - PubMed
  224. J Alzheimers Dis. 2017;56(2):775-788 - PubMed
  225. CPT Pharmacometrics Syst Pharmacol. 2017 Feb;6(2):73-86 - PubMed
  226. Nat Neurosci. 2017 Feb;20(2):145-155 - PubMed
  227. Circ Res. 2017 Feb 3;120(3):502-513 - PubMed
  228. Sci Rep. 2017 Feb 08;7:41802 - PubMed
  229. Lab Anim (NY). 2017 Mar 22;46(4):103-113 - PubMed
  230. Neurology. 2017 Apr 18;88(16):1556-1563 - PubMed
  231. Europace. 2018 Mar 1;20(3):408-419 - PubMed
  232. Kidney Res Clin Pract. 2017 Mar;36(1):3-11 - PubMed
  233. Genome Biol. 2017 Apr 13;18(1):70 - PubMed
  234. EBioMedicine. 2017 Jul;21:21-28 - PubMed
  235. Neuron. 2017 Apr 19;94(2):278-293.e9 - PubMed
  236. Annu Rev Neurosci. 2017 Jul 25;40:251-272 - PubMed
  237. J Alzheimers Dis. 2017;58(2):355-359 - PubMed
  238. Dis Model Mech. 2017 May 1;10(5):499-502 - PubMed
  239. Front Cell Neurosci. 2017 Apr 28;11:120 - PubMed
  240. Lancet Neurol. 2017 Jun;16(6):478-488 - PubMed
  241. Acta Neuropathol. 1988;76(3):217-221 - PubMed
  242. Biochem J. 2017 May 16;474(11):1823-1836 - PubMed
  243. Nat Rev Neurosci. 2017 Jul;18(7):419-434 - PubMed
  244. Sci Rep. 2017 May 25;7(1):2426 - PubMed
  245. Am Heart J. 2017 Jun;188:93-98 - PubMed
  246. Nat Commun. 2017 Jun 20;8(1):24 - PubMed
  247. Epilepsy Behav. 2017 Jul;72:188-194 - PubMed
  248. Sci Rep. 2017 Jul 5;7(1):4716 - PubMed
  249. J Cell Biochem. 2018 Feb;119(2):1249-1256 - PubMed
  250. Front Cell Neurosci. 2017 Jul 04;11:180 - PubMed
  251. Lancet. 2017 Dec 16;390(10113):2673-2734 - PubMed
  252. J Cereb Blood Flow Metab. 2017 Nov;37(11):3488-3517 - PubMed
  253. Psychol Med. 2017 Nov;47(15):2587-2592 - PubMed
  254. Antioxidants (Basel). 2017 Aug 18;6(3):null - PubMed
  255. Curr Atheroscler Rep. 2017 Aug 25;19(10):39 - PubMed
  256. Lancet Gastroenterol Hepatol. 2017 Oct;2(10):747-756 - PubMed
  257. Alzheimers Res Ther. 2017 Sep 12;9(1):71 - PubMed
  258. Lancet Neurol. 2017 Nov;16(11):877-897 - PubMed
  259. Heart Rhythm. 2018 Feb;15(2):166-172 - PubMed
  260. Neuron. 2017 Sep 27;96(1):17-42 - PubMed
  261. J Alzheimers Dis. 2017;60(4):1241-1257 - PubMed
  262. PLoS One. 2017 Nov 1;12(11):e0187307 - PubMed
  263. Biochem Biophys Res Commun. 2018 Jan 1;495(1):533-538 - PubMed
  264. Hypertension. 2018 Jun;71(6):e13-e115 - PubMed
  265. Nat Commun. 2017 Nov 24;8(1):1778 - PubMed
  266. Mov Disord. 2018 Mar;33(3):349-358 - PubMed
  267. Exp Neurobiol. 2017 Dec;26(6):369-379 - PubMed
  268. J Neuroinflammation. 2018 Jan 08;15(1):8 - PubMed
  269. Front Aging Neurosci. 2017 Dec 12;9:407 - PubMed
  270. Sci Rep. 2018 Jan 11;8(1):430 - PubMed
  271. Cell. 2018 Jan 11;172(1-2):262-274.e11 - PubMed
  272. Cell. 2018 Jan 11;172(1-2):275-288.e18 - PubMed
  273. Sci Rep. 2018 Jan 12;8(1):568 - PubMed
  274. Brain Res. 2018 Aug 15;1693(Pt B):207-213 - PubMed
  275. Nat Rev Neurol. 2018 Mar;14(3):133-150 - PubMed
  276. Cell Rep. 2018 Jan 23;22(4):930-940 - PubMed
  277. J Clin Invest. 2018 Apr 2;128(4):1208-1216 - PubMed
  278. J Alzheimers Dis. 2018;62(2):549-560 - PubMed
  279. Sci Rep. 2018 Mar 20;8(1):4907 - PubMed
  280. Microbiome. 2018 Mar 21;6(1):55 - PubMed
  281. Trends Neurosci. 2018 Jun;41(6):360-372 - PubMed
  282. Neuroimage. 2018 Jul 15;175:246-258 - PubMed
  283. Mater Sci Eng C Mater Biol Appl. 2018 Aug 1;89:194-204 - PubMed
  284. Acta Neuropathol. 2018 Jul;136(1):89-110 - PubMed
  285. J Alzheimers Dis. 2018;63(4):1337-1346 - PubMed
  286. J Cereb Blood Flow Metab. 2018 Aug;38(8):1293-1298 - PubMed
  287. Mol Psychiatry. 2019 Feb;24(2):266-281 - PubMed
  288. Curr Allergy Asthma Rep. 2018 Jun 15;18(8):42 - PubMed
  289. J Alzheimers Dis. 2018;64(2):657-668 - PubMed
  290. Science. 2018 Jun 22;360(6395): - PubMed
  291. FASEB J. 2018 Jun 22;:fj201800597R - PubMed
  292. Cell Rep. 2018 Jul 24;24(4):973-986.e8 - PubMed
  293. Nat Commun. 2018 Aug 24;9(1):3434 - PubMed
  294. Neurochem Int. 2018 Nov;120:191-199 - PubMed
  295. Pain. 2019 Jan;160(1):210-223 - PubMed
  296. J Mol Med (Berl). 2018 Nov;96(11):1153-1166 - PubMed
  297. Nature. 2018 Oct;562(7728):578-582 - PubMed
  298. Nat Neurosci. 2018 Oct;21(10):1370-1379 - PubMed
  299. Nat Neurosci. 2018 Oct;21(10):1300-1309 - PubMed
  300. Int J Mol Sci. 2018 Sep 27;19(10):null - PubMed
  301. Stem Cell Res Ther. 2018 Oct 11;9(1):266 - PubMed
  302. Front Neurosci. 2018 Oct 09;12:726 - PubMed
  303. Neurology. 1987 Jul;37(7):1253-5 - PubMed
  304. Mol Brain. 2018 Nov 14;11(1):68 - PubMed
  305. J Exp Med. 2018 Dec 3;215(12):2955-2958 - PubMed
  306. J Alzheimers Dis. 2018;66(4):1657-1682 - PubMed
  307. Nat Commun. 2018 Nov 26;9(1):4974 - PubMed
  308. Cell Metab. 2019 May 7;29(5):1061-1077.e8 - PubMed
  309. J Extracell Vesicles. 2018 Nov 23;7(1):1535750 - PubMed
  310. Free Radic Biol Med. 2019 Apr;134:695-701 - PubMed
  311. JAMA Netw Open. 2018 Oct 5;1(6):e183597 - PubMed
  312. Physiol Rev. 2019 Apr 1;99(2):1047-1078 - PubMed
  313. J Gerontol A Biol Sci Med Sci. 2019 Jan 14;:null - PubMed
  314. Front Neurosci. 2019 Jan 24;13:2 - PubMed
  315. Alzheimers Dement (Amst). 2019 Feb 28;11:205-215 - PubMed
  316. J Intern Med. 2019 Jul;286(1):101-110 - PubMed
  317. Arch Gen Psychiatry. 1969 Aug;21(2):240-8 - PubMed
  318. Brain Res. 1984 Jan 30;292(1):23-32 - PubMed
  319. Psychopharmacology (Berl). 1984;83(1):1-16 - PubMed
  320. Am J Physiol. 1983 Mar;244(3):H406-12 - PubMed
  321. Neurology. 1995 May;45(5):883-8 - PubMed
  322. Cell. 1994 Sep 23;78(6):919-25 - PubMed
  323. Mod Pathol. 1993 Jan;6(1):10-4 - PubMed
  324. Adv Pharmacol. 1995;34:155-70 - PubMed
  325. Nature. 1996 Mar 14;380(6570):168-71 - PubMed
  326. J Neural Transm Suppl. 1995;46:139-47 - PubMed
  327. JAMA. 1997 Mar 12;277(10):813-7 - PubMed
  328. Lancet. 1997 Jan 18;349(9046):151-4 - PubMed
  329. Adv Exp Med Biol. 1997;413:155-9 - PubMed
  330. Adv Exp Med Biol. 1997;413:177-93 - PubMed
  331. Cell. 1997 Dec 26;91(7):917-25 - PubMed
  332. Physiol Rev. 1998 Jan;78(1):53-97 - PubMed

Publication Types