TY - JOUR
T1 - Amyotrophic lateral sclerosis
T2 - The complement and inflammatory hypothesis
AU - Kjældgaard, Anne-Lene
AU - Pilely, Katrine
AU - Olsen, Karsten Skovgaard
AU - Pedersen, Stephen Wørlich
AU - Lauritsen, Anne Øberg
AU - Møller, Kirsten
AU - Garred, Peter
N1 - Copyright © 2018 Elsevier Ltd. All rights reserved.
PY - 2018/10
Y1 - 2018/10
N2 - Amyotrophic lateral sclerosis (ALS) is a devastating, neurodegenerative motor neuron disease. The aetiology of ALS remains an enigma which hinders the design of an effective treatment to prevent, postpone, or reverse the pathophysiological changes occurring during the aggressive progression of this disease. During the last decade, basic research within the innate immune system, and in particular the complement system, has revealed new, important roles of the innate immune system during development, homeostasis, and ageing within as well as outside the central nervous system. Several lines of evidence indicate that aberrant activation of the complement system locally in the central nervous system as well as systemically may be involved in the pathophysiology of ALS. This exciting new knowledge could point towards the innate immune system as a potential target of medical intervention in ALS. Recently, the historic perception of ALS as a central neurodegenerative disease has been challenged due to the significant amount of evidence of a dying-back mechanism causing the selective destruction of the motor neurons, indicating that disease onset occurs outside the borders of the blood-brain-barrier. This review addresses the function of the innate immune system during ALS. We emphasize the role of the complement system and specifically suggest the involvement of ficolin-3 from the lectin pathway in the pathophysiology of ALS.
AB - Amyotrophic lateral sclerosis (ALS) is a devastating, neurodegenerative motor neuron disease. The aetiology of ALS remains an enigma which hinders the design of an effective treatment to prevent, postpone, or reverse the pathophysiological changes occurring during the aggressive progression of this disease. During the last decade, basic research within the innate immune system, and in particular the complement system, has revealed new, important roles of the innate immune system during development, homeostasis, and ageing within as well as outside the central nervous system. Several lines of evidence indicate that aberrant activation of the complement system locally in the central nervous system as well as systemically may be involved in the pathophysiology of ALS. This exciting new knowledge could point towards the innate immune system as a potential target of medical intervention in ALS. Recently, the historic perception of ALS as a central neurodegenerative disease has been challenged due to the significant amount of evidence of a dying-back mechanism causing the selective destruction of the motor neurons, indicating that disease onset occurs outside the borders of the blood-brain-barrier. This review addresses the function of the innate immune system during ALS. We emphasize the role of the complement system and specifically suggest the involvement of ficolin-3 from the lectin pathway in the pathophysiology of ALS.
U2 - 10.1016/j.molimm.2018.06.007
DO - 10.1016/j.molimm.2018.06.007
M3 - Journal article
C2 - 29933890
SN - 0161-5890
VL - 102
SP - 14
EP - 25
JO - Molecular Immunology
JF - Molecular Immunology
ER -