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Tryptophan Metabolism in Alzheimer's Disease with the Involvement of Microglia and Astrocyte Crosstalk and Gut-Brain Axis.
Xie, Lushuang; Wu, Qiaofeng; Li, Kelin; Khan, Mohammed A S; Zhang, Andrew; Sinha, Bharati; Li, Sihui; Chang, Sulie L; Brody, David L; Grinstaff, Mark W; Zhou, Shuanhu; Alterovitz, Gil; Liu, Pinghua; Wang, Xin.
Afiliación
  • Xie L; Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Wu Q; Acupuncture and Moxibustion College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610075, China.
  • Li K; Acupuncture and Moxibustion College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610075, China.
  • Khan MAS; Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Zhang A; Department of Chemistry, Boston University, Boston, MA 02215, USA.
  • Sinha B; Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Li S; Biomedical Cybernetics Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Chang SL; Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Brody DL; Acupuncture and Moxibustion College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610075, China.
  • Grinstaff MW; Department of Biological Sciences, Institute of NeuroImmune Pharmacology, Seton Hall University, South Orange, NJ 07079, USA.
  • Zhou S; Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
  • Alterovitz G; Department of Chemistry, Boston University, Boston, MA 02215, USA.
  • Liu P; Harvard Medical School, Harvard Stem Cell Institute, Boston, MA 02115, USA.
  • Wang X; Biomedical Cybernetics Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Aging Dis ; 15(5): 2168-2190, 2024 Oct 01.
Article en En | MEDLINE | ID: mdl-38916729
ABSTRACT
Alzheimer's disease (AD) is an age-dependent neurodegenerative disease characterized by extracellular Amyloid Aß peptide (Aß) deposition and intracellular Tau protein aggregation. Glia, especially microglia and astrocytes are core participants during the progression of AD and these cells are the mediators of Aß clearance and degradation. The microbiota-gut-brain axis (MGBA) is a complex interactive network between the gut and brain involved in neurodegeneration. MGBA affects the function of glia in the central nervous system (CNS), and microbial metabolites regulate the communication between astrocytes and microglia; however, whether such communication is part of AD pathophysiology remains unknown. One of the potential links in bilateral gut-brain communication is tryptophan (Trp) metabolism. The microbiota-originated Trp and its metabolites enter the CNS to control microglial activation, and the activated microglia subsequently affect astrocyte functions. The present review highlights the role of MGBA in AD pathology, especially the roles of Trp per se and its metabolism as a part of the gut microbiota and brain communications. We (i) discuss the roles of Trp derivatives in microglia-astrocyte crosstalk from a bioinformatics perspective, (ii) describe the role of glia polarization in the microglia-astrocyte crosstalk and AD pathology, and (iii) summarize the potential of Trp metabolism as a therapeutic target. Finally, we review the role of Trp in AD from the perspective of the gut-brain axis and microglia, as well as astrocyte crosstalk, to inspire the discovery of novel AD therapeutics.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Triptófano / Astrocitos / Microglía / Enfermedad de Alzheimer / Microbioma Gastrointestinal / Eje Cerebro-Intestino Límite: Animals / Humans Idioma: En Revista: Aging Dis Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Triptófano / Astrocitos / Microglía / Enfermedad de Alzheimer / Microbioma Gastrointestinal / Eje Cerebro-Intestino Límite: Animals / Humans Idioma: En Revista: Aging Dis Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos