Lipocalin 2 as a link between ageing, risk factor conditions and age-related brain diseases

Doortje W Dekens; Ulrich L M Eisel; Leonie Gouweleeuw; Regien G Schoemaker; Peter P De Deyn; Petrus J W Naudé

doi:10.1016/j.arr.2021.101414

Lipocalin 2 as a link between ageing, risk factor conditions and age-related brain diseases

Ageing Res Rev. 2021 Sep:70:101414. doi: 10.1016/j.arr.2021.101414. Epub 2021 Jul 26.

Authors

Doortje W Dekens¹, Ulrich L M Eisel², Leonie Gouweleeuw², Regien G Schoemaker², Peter P De Deyn³, Petrus J W Naudé⁴

Affiliations

¹ Department of Neurology and Alzheimer Center Groningen, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; Department of Molecular Neurobiology, Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Groningen, the Netherlands.
² Department of Molecular Neurobiology, Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Groningen, the Netherlands.
³ Department of Neurology and Alzheimer Center Groningen, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; Laboratory of Neurochemistry and Behaviour, Biobank, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
⁴ Department of Neurology and Alzheimer Center Groningen, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; Department of Molecular Neurobiology, Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Groningen, the Netherlands; Department of Psychiatry and Mental Health and Neuroscience Institute, Brain Behaviour Unit, University of Cape Town, Cape Town, South Africa. Electronic address: p.j.w.naude@umcg.nl.

PMID: 34325073
DOI: 10.1016/j.arr.2021.101414

Abstract

Chronic (neuro)inflammation plays an important role in many age-related central nervous system (CNS) diseases, including Alzheimer's disease, Parkinson's disease and vascular dementia. Inflammation also characterizes many conditions that form a risk factor for these CNS disorders, such as physical inactivity, obesity and cardiovascular disease. Lipocalin 2 (Lcn2) is an inflammatory protein shown to be involved in different age-related CNS diseases, as well as risk factor conditions thereof. Lcn2 expression is increased in the periphery and the brain in different age-related CNS diseases and also their risk factor conditions. Experimental studies indicate that Lcn2 contributes to various neuropathophysiological processes of age-related CNS diseases, including exacerbated neuroinflammation, cell death and iron dysregulation, which may negatively impact cognitive function. We hypothesize that increased Lcn2 levels as a result of age-related risk factor conditions may sensitize the brain and increase the risk to develop age-related CNS diseases. In this review we first provide a comprehensive overview of the known functions of Lcn2, and its effects in the CNS. Subsequently, this review explores Lcn2 as a potential (neuro)inflammatory link between different risk factor conditions and the development of age-related CNS disorders. Altogether, evidence convincingly indicates Lcn2 as a key constituent in ageing and age-related brain diseases.

Keywords: Chronic inflammation; Inflammageing; Lifestyle; Neurodegenerative disease; Neuroinflammation; Neutrophil gelatinase-associated lipocalin (NGAL).

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Acute-Phase Proteins / metabolism
Alzheimer Disease*
Humans
Lipocalin-2
Lipocalins*
Risk Factors

Substances

Acute-Phase Proteins
LCN2 protein, human
Lipocalin-2
Lipocalins