TY - JOUR
T1 - Inhibition of colony stimulating factor-1 receptor (CSF-1R) as a potential therapeutic strategy for neurodegenerative diseases
T2 - opportunities and challenges
AU - Han, Jinming
AU - Chitu, Violeta
AU - Stanley, E. Richard
AU - Wszolek, Zbigniew K.
AU - Karrenbauer, Virginija Danylaité
AU - Harris, Robert A.
N1 - Funding Information:
Open access funding provided by Karolinska Institute. This work was supported by grants from the Swedish Medical Research Council, Neuroforbundet, Alltid Lite Sterkere, HjärnFonden, AlzheimerFonden and BarnCancerFonden. ZKW is partially supported by the Mayo Clinic Center for Regenerative Medicine, the gifts from The Sol Goldman Charitable Trust, and the Donald G. and Jodi P. Heeringa Family, the Haworth Family Professorship in Neurodegenerative Diseases Fund, and The Albertson Parkinson’s Research Foundation. ERS and VC have received financial support from NIH grants: R01NS091519, U54 HD090260 and P30CA013330 and from David and Ruth Levine.
Funding Information:
ZKW serves as PI or Co-PI on Biogen, Inc. (228PD201), Biohaven Pharmaceuticals, Inc. (BHV4157-206 and BHV3241-301), and Neuraly, Inc. (NLY01-PD-1) grants. He serves as Co-PI of the Mayo Clinic APDA Center for Advanced Research. VDK Biogen (recipient of grant and scholarship, PI for project sponsored by); Novartis (Scientific Advisory board member, recipient of scholarship and lecture honoraria); Merc (Scientific Advisory Board member, recipient of lecture honoraria), Neuro Vigil (Scientific Advisory Board member). VDK has received financial support from Stockholm County Council (Grant ALF 20160457), Biogen (recipient of grant and scholarship, PI for the project sponsored by Biogen); Novartis (Scientific Advisory Board member, recipient of scholarship and lecture honoraria) and Merck (Scientific Advisory Board member, recipient of lecture honoraria).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/4
Y1 - 2022/4
N2 - Microglia are specialized dynamic immune cells in the central nervous system (CNS) that plays a crucial role in brain homeostasis and in disease states. Persistent neuroinflammation is considered a hallmark of many neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson's disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS) and primary progressive multiple sclerosis (MS). Colony stimulating factor 1-receptor (CSF-1R) is predominantly expressed on microglia and its expression is significantly increased in neurodegenerative diseases. Cumulative findings have indicated that CSF-1R inhibitors can have beneficial effects in preclinical neurodegenerative disease models. Research using CSF-1R inhibitors has now been extended into non-human primates and humans. This review article summarizes the most recent advances using CSF-1R inhibitors in different neurodegenerative conditions including AD, PD, HD, ALS and MS. Potential challenges for translating these findings into clinical practice are presented.
AB - Microglia are specialized dynamic immune cells in the central nervous system (CNS) that plays a crucial role in brain homeostasis and in disease states. Persistent neuroinflammation is considered a hallmark of many neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson's disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS) and primary progressive multiple sclerosis (MS). Colony stimulating factor 1-receptor (CSF-1R) is predominantly expressed on microglia and its expression is significantly increased in neurodegenerative diseases. Cumulative findings have indicated that CSF-1R inhibitors can have beneficial effects in preclinical neurodegenerative disease models. Research using CSF-1R inhibitors has now been extended into non-human primates and humans. This review article summarizes the most recent advances using CSF-1R inhibitors in different neurodegenerative conditions including AD, PD, HD, ALS and MS. Potential challenges for translating these findings into clinical practice are presented.
KW - Alzheimer’s disease
KW - Amyotrophic lateral sclerosis
KW - Colony stimulating factor-1 receptor
KW - Huntington’s disease
KW - Multiple sclerosis
KW - Parkinson’s disease
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U2 - 10.1007/s00018-022-04225-1
DO - 10.1007/s00018-022-04225-1
M3 - Review article
C2 - 35366105
AN - SCOPUS:85127392316
SN - 1420-682X
VL - 79
JO - Cellular and Molecular Life Sciences
JF - Cellular and Molecular Life Sciences
IS - 4
M1 - 219
ER -
