Table 1.
Expression and potential roles of TLR in neurodegenerative conditions.
| TLR | Expression in diseases | Potential role | References | |
|---|---|---|---|---|
| Protective | Deleterious | |||
| ↑AD, PD and ALS patients | N.A. | N.A. | Letiembre et al. (2009), Casula et al. (2011) and Doorn et al. (2014) | |
| APP (AD mouse model) | TLR2 deficiency impaired Aβ clearance | N.A. | Drouin-Ouellet and Cicchetti (2012) | |
| TLR2 | ↑APP23 (AD mouse model) | N.A. | Increased expression associated with Aβ-plaques deposition. | Frank et al. (2009) |
| ↑in microglia (neuron-released α-synuclein) | N.A. | Induced neurodegeneration. | Kim et al. (2013) | |
| ↑LPS-stimulated SOD1 G37R (ALS mouse model) | N.A. | Degeneration of motor neurons and motor axons. | Nguyen et al. (2004) | |
| TLR3 | ↑MS patients | N.A. | N.A. | Bsibsi et al. (2002) |
| TLR4 | ↑AD, PD and ALS patients | N.A | N.A | Letiembre et al. (2009), Casula et al. (2011) and Drouin-Ouellet et al. (2015) |
| ↑APP (AD mouse model) | Boosted Aβ clearance and preserved cognition | N.A. | Herber et al. (2006), Song et al. (2011) and Sarlus and Heneka (2017) | |
| ↑APP (AD mouse model) | N.A. | Increased expression associated with Aβ-plaques deposition. | Walter et al. (2007) | |
| SOD1 G93A (ALS mouse model) | N.A. | TLR4 deficiency improved motor performance and extended life expectancy. | Lee et al. (2015) | |
| ↑AD, OPCA and PID patients | N.A. | N.A. | Bsibsi et al. (2002) | |
| ↑MSA patients | N.A. | N.A. | Brudek et al. (2013) | |
| TLR5 | ↑genetic PD mouse model | N.A. | N.A. | Letiembre et al. (2009) |
| ↓PD rat model | N.A. | Cognitive and motivational behavior impairment. | Viana et al. (2017) | |
| TLR7 | ↑AD, PD, OPCA and PID patients | N.A. | N.A. | Bsibsi et al. (2002) |
| ↑genetic mice models of AD, ALS | N.A. | N.A. | Letiembre et al. (2009) | |
| ↑genetic mice models of AD | N.A. | Deletion of TLR7 improved spatial learning. | Liu et al. (2017) | |
| ↑TLR7 (loxoribine) in co-culture of microglia and neurons | N.A. | Loss of neurons, axonal injury in the cerebral cortex and pronounced microglia activation in the mouse brain. | Rosenberger et al. (2014) | |
| ↑TLR7 (microRNA let-7) in mouse | N.A. | Induced neurodegeneration. | Lehmann et al. (2012a) | |
| ↑TLR7 (ssRNA40) in mouse | N.A. | Induced neuronal cell death. | Lehmann et al. (2012b) | |
| TLR9 | ↑PD patients, mouse PD and ALS models | N.A. | N.A. | Letiembre et al. (2009) and Ros-Bernal et al. (2011) |
| ↑TLR9 (CpG-DNA) in co-culture of microglia and neurons | N.A. | Neuronal toxicity. | Iliev et al. (2004) | |
| ↑TLR9 (CpG-DNA) in mouse | N.A. | Impairment in spatial memory, microglial activation and acute axonal damage. | Tauber et al. (2009) | |
| ↑TLR9 (CpG-DNA) in mouse | N.A. | Loss of neurons, axonal injury in the cerebral cortex and pronounced microglia activation. | Rosenberger et al. (2014) | |
| ↑Late phase of MS mouse model | N.A. | Deletion of TLR9 reduced inflammation, demyelination and axonal damage. | Prinz et al. (2006) | |
| ↑TLR9 in a PD mouse model | N.A. | Induced dopaminergic neurons loss. | Maatouk et al. (2018) | |
| ↑TLR9 (CpG-DNA) in AD model | Aβ ingestion by microglia, which reduces Aβ aggregation and improve the memory impairment in mice | N.A. | Iribarren et al. (2005), Tahara et al. (2006), Doi et al. (2009) and Scholtzova et al. (2009) | |
| ↑TLR9 (DNA degenerating neurons) in mouse model of epilepsy | Attenuation of aberrant neurogenesis in the hippocampus and reduced seizure | TNF-α expression | Matsuda et al. (2015) | |
↑increase; ↓decrease; N.A. - not available.