Table 1 Potential markers of reactive astrocytes

From: Reactive astrocyte nomenclature, definitions, and future directions

Marker	Known function	Type of change	Conditions observed	Species	Comments	Ref.
Cytoskeleton
GFAP	Intermediate filament	↑ mRNA & protein	Widespread. Not in some trauma models	Widespread	Released by injured astrocytes. Cleavage product found in CSF and plasma (neurotrauma biomarker)	¹²²
Nestin	Intermediate filament	↑ mRNA & protein	AD, AxD, MS, SCI, TBI	Hu, Ms	Also a marker of progenitor cells	¹²³
Synemin	Intermediate filament	↑ mRNA & protein	AD, AxD, astrocytoma, TBI	Hu, Ms	Normally expressed in a subset of astrocytes during development	¹²⁴
Vimentin	Intermediate filament	↑ mRNA & protein	Widespread	Widespread	Also expressed by endothelial cells, vascular smooth muscle cells, and immature astrocytes	¹²⁵
Metabolism
ALDOC	Glycolytic enzyme	↑ protein	SCI, TBI	Hu, Ms	Released by injured astrocytes. Fluid biomarker for neurotrauma	^30,31
BLBP/ FABP7	Lipid transport	↑ protein	AD, MS, TBI	Hu, Ms	Also a marker of immature astrocytes. Released by injured astrocytes. Fluid biomarker for neurotrauma	^31,60
MAO-B	Catecholamine catabolic enzyme	↑ protein	AD, ALS, PD	Hu, Ms	PET radiotracers available. Also expressed by catecholaminergic neurons	^63,64,117
TSPO	Mitochondrial lipid transporter	↑ mRNA & protein	AD, MS, ischemia	Hu, Rt, Ms	PET radiotracers available. Also induced in reactive microglia. Expressed by vascular cells	¹²⁶
Chaperones
CRYAB	Chaperone activity	↑ mRNA & protein, ↑ secretion	AD, AxD, epilepsy, HD, MS, TBI	Hu, Ms	Reduces protein aggregation	^74,95
HSPB1/HSP27	Chaperone	↑ mRNA & protein	AD, AxD, epilepsy, MS, tauopathies, stroke	Widespread		^95,127
Secreted proteins
C3	Complement factor	↑ mRNA & protein	ND, prion disease, septic shock	Hu, Ms	Also expressed by microglia	⁷²
CHI3L1/ YKL40	Unclear function	↑ mRNA & protein, ↑ secretion	Widespread	Hu, Ms	Increase in CSF is a prognostic biomarker in LOAD and MS	^79,115
Lcn2	Iron trafficking protein	↑ mRNA & protein	AxD, MS, septic shock, ALS, stroke	Widespread		⁶⁶
Serpina3n/ACT	Serine protease inhibitor	↑ mRNA	AD, septic shock, stroke	Hu, Ms	Secreted to extracellular matrix	⁶⁶
MT	Metal binding	↑ mRNA & protein	HD, PD, AD	Hu, Ms	Antioxidant effects	⁷⁴
THBS-1	Synaptogenic factor	↑ mRNA & protein, ↑ secretion	Axotomy, MS	Hu, Ms	STAT3-regulated. Has beneficial synaptogenic effects	⁵⁰
Cell signaling – transcription factors
NFAT	Transcription factor	↑ mRNA, protein, nuclear translocation	AD, TBI, PD	Hu, Ms	Links Ca²⁺ signaling with reactive transcriptional changes	^38,128
NTRK2/ TrkB IL17R	Receptors	↑ mRNA and/or protein	Epilepsy, MS (white matter)	Hu, Ms	Trigger non-canonical pathological BDNF-dependent signaling, and/or NF-κB activation and NO production	^33,109
S100B	Ca²⁺ binding protein	↑ protein and release	Widespread	Widespread	Released upon injury. Fluid biomarker	¹²⁹
SOX9	Transcription factor	↑ mRNA and/or protein	ALS, stroke, SCI	Hu, Ms	Nuclear staining. Also present in ependymal cells and in neurogenic niches	¹³⁰
STAT3	Transcription factor	Phosphorylation, nuclear translocation	Widespread	Widespread	Also expressed in neurons and other cell types	^49,50,131
Channels – Transporters
EAAT1 & 2	Glutamate transporters	↓ mRNA, protein and uptake	ND	Widespread	May be also detected in some neuronal cells	^53,132
KIR4.1	K⁺ channel	↓ mRNA & protein	Widespread	Hu, Ms	May or may not translate into alteration of K⁺ buffering	⁵⁸

This table lists potential markers for reactive astrocytes in different pathological contexts in human diseases and animal models. The list is not meant to be exhaustive; other markers exist and more will be added over time. These proteins can be used to further characterize the reactive state of astrocytes, although note that, like GFAP (see ‘GFAP as a marker’), none of these proteins should be used as a single or universal marker of reactive astrocytes, nor for the time being do they identify a specific type of reactive astrocyte. Plausibly, markers in this table will be part of signatures defining disease-specific or core markers of reactive astrocytes, as well as astrocyte-based fluid biomarkers (see ‘Toward astrocyte-targeting therapies’). Importantly, few of these markers are astrocyte-specific; therefore, additional methods to identify or isolate astrocytes and remove contamination by other cell types will be in order.
AxD, Alexander disease; BDNF, brain-derived neurotrophic factor; CSF, cerebrospinal fluid; Hu, human; LOAD, late-onset AD; Ms, mouse; ND, neurodegenerative disease; NO, nitric oxide; Rt, rat; SCI, spinal cord injury; TBI, traumatic brain injury.

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Table 1 Potential markers of reactive astrocytes

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