Neuroimmune crosstalk in neurodegeneration: ALS and FTD

Our lab is interested in defining neuroimmune mechanisms in neurodegeneration. Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal dementia (FTD) are fatal neurodegenerative diseases whose underlying mechanisms are under intense investigation. Microglia and other immune cells are activated in brains and spinal cords of patients with ALS and mouse models of ALS. We have previously identified specific innate and adaptive immune transcriptional signatures of immune cells in ALS mice, and found that T cells regulate disease progression in mutant SOD1 mice. Microglia likely turn on both neuroprotective and harmful signatures in ALS mice. Many questions still remain in these disease conditions. In our lab, we are studying in particular the role of inflammatory cell death pathways both in neurons and in microglia in regulating the outcome of ALS and FTD. We are also interested in whether peripheral inflammatory triggers such as microbial or immune factors could contribute to ALS outcome. Dr. Chiu had done his PhD and postdoctoral work on this project. While it is still relatively new to his lab, neurodegeneration is a growing area of research in his group.

Publications on this topic:

  1. Chiu IM*, Chen A, Zheng Y,Kosaras B, Tsiftsoglou SA, Vartanian TK, Brown RH Jr, *Carroll MC. T lymphocytes potentiate endogenous neuro-protective inflammation in a mouse model of ALS. Proc. Natl. Acad. Sci. USA. 2008 Nov 18; 106(46):17913-17918. PMCID: PMC2581614. *Co-corresponding authors.  PDF
  2. Chiu IM, Phatnani H, Kuligowski M, Tapia JC, Carrasco MA, Zhang M, Maniatis T, Carroll MC. Activation of innate and humoral immunity in the peripheral nervous system of ALS transgenic mice. Proc. Natl. Acad. Sci. USA. 2009 Dec 8; 106(49):20960-20965. PMCID: PMC2791631.  PDF
  3. Chiu IM, Morimoto ET, Goodarzi H, Liao JT, O’Keefe S, Phatnani HP, Carroll MC, Levy, S, Tavazoie S, Myers RM, Maniatis T. A neurodegeneration-specific gene-expression signature of acutely isolated microglia from an amyotrophic lateral sclerosis mouse model. Cell Reports. 2013 Jul 25; 4(2):385-401. PMCID: PMC4272581.  PDF