Table 1.
Regulation of adenosine homeostasis-related proteins in neurodegenerative diseases
| Disease | Component | Effect | Model | Clinical (C)/Preclinical (P) | References |
|---|---|---|---|---|---|
| AD | ADA | Up | Activity in AD patients | C | [8] |
| Up | Thy-Tau22 mouse model | P | [46] | ||
| ADK | Up | Protein level in AD patients | C | [25] | |
| CD39 | Up | APP/PS1 mouse model | P | [19] | |
| Up | Thy-Tau22 mouse model | P | [46] | ||
| CD73 | Up | Activity in β-amyloid (Aβ1-42)-based mouse model of early AD | P | [93] | |
| Up | Thy-Tau22 mouse model | P | [46] | ||
| AMPK | Up | AMPKα1 in AD patients | C | [262] | |
| Down | AMPKα2 in AD patients | C | [262] | ||
| Up | AMPKα1 in Tg19959 mouse model | P | [262] | ||
| Up | Activity in AD patients | C | [162] | ||
| Up | Activity in APP/PS1 mouse model | P | [162] | ||
| Up | Activity in Thy-Tau22 mouse model | P | [46] | ||
| Down | Activity in APP/PS1 mouse model | P | [232] | ||
| Down | Activity in STZ-treated mouse model | P | [232] | ||
| PD | ADA | Up | Transcript level in the frontal cortex of PD patients at stages 3–4 | C | [90] |
| Up | Activity in the serum from PD patients | C | [51, 52] | ||
| Up | Activity in the striatum of MPTP mouse model | P | [114] | ||
| CD73 | Up | Transcript level in the frontal cortex of PD patients at stages 5–6 | C | [90] | |
| Up | Protein level in striatal synaptosome of a 6-OHDA rat model | P | [38] | ||
| Up | Protein level in 6-OHDA-treated differentiated SH-SY5Y cells | P | [38] | ||
| AMPK | Down | Total and phosphorylated levels in the substantia nigra of MPTP-treated mice and in MPP+-treated PC12 cells | P | [215] | |
| Unchanged | Total and phosphorylated levels in the substantia nigra of MPTP-treated mice | P | [249] | ||
| Up | Phosphorylated level in the substantia nigra of MPTP-treated mice | P | [149] | ||
| Up | Phosphorylated level in the substantia nigra of patients with dementia with Lewy bodies and of MPTP-treated and α-synuclein-overexpressing mice | P | [126] | ||
| HD | ENT1 | Up | HD patients | C | [99] |
| Up | R6/2 mouse model | P | [127] | ||
| Up | Hdh150Q mouse model | P | [127] | ||
| Up | zQ175 mouse model | P | [99] | ||
| ENT2 | Up | R6/2 mouse model | P | [127] | |
| Up | Hdh150Q mouse model | P | [127] | ||
| ADA | Up | Activity in HEK 293 T cell line transfected with mutant exon 1 of the HTT gene | P | [217] | |
| ADK | Up | R6/2 mouse model | P | [127] | |
| CD39 | Down | Activity in HEK 293 T cell line transfected with mutant exon 1 of the HTT gene | P | [217] | |
| CD73 | Down | Activity in HEK 293 T cell line transfected with mutant exon 1 of the HTT gene | P | [217] | |
| AMPK | Up | Activity in HD patients | C | [125] | |
| Up | Activity in R6/2 mouse model | P | [125] | ||
| ALS | ADA | Down | ALS patients-derived astrocyte | P | [7] |
| ADK | Up | Activity in reactive astrocytes of ALS patients | C | [25] | |
| CD39 | Down | Transcript level in ALS patients | C | [33] | |
| Down | Transcript and protein level in SOD1(G93A) mouse model | P | [33, 230] | ||
| CD73 | Up | SOD1(G93A) mouse model | P | [87] | |
| AMPK | Down | ALS patients-derived BM-MSC | P | [256] | |
| Up | Activity in ALS patients | C | [155, 156] | ||
| Up | Activity in SOD1(G93A) mouse model | P | [153, 257] | ||
| Up | Activity in TDP-43 mouse model | P | [155] | ||
| Epilepsy | ENT1 | Up | Protein level in neocortex of patients with temporal lobe epilepsy | C | [248] |
| Up | Protein level in the hippocampus of a pilocarpine-induced rat model | P | [248] | ||
| ADK | Up | Protein level in temporal lobe of patients with epilepsy | C | [13, 165] | |
| Up | Protein level in the hippocampus and astrocytes of a kainite mouse model | P | [96] | ||
| Up | Protein level in the hippocampus, cortex, and astrocytes of rats with status epilepticus | P | [13] | ||
| AMPK | Down | Protein level in the neocortex of epileptic patients | C | [252] | |
| Down | Protein level in the hippocampus of pentylenetetrazol- and kainic acid-induced mouse models | P |
6-OHDA, 6-hydroxydopamine; ADA, adenosine deaminase; ADK, adenosine kinase; AMPK, AMP-activated protein kinase; BM-MSC, Bone marrow mesenchymal stem cells; ENT1, equilibrative nucleoside transporter 1; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; MPP+, 1-methyl-4-phenylpyridinium; STZ, Streptozotocin