Table 1.
Summary of the main targets of cdk5 in neurological diseases and mechanism of Cdk5 and nervous system diseases.
| Targets or Pathways | References | ||
|---|---|---|---|
| Nervous system diseases | Alzheimer’s disease | Aβ generation: Cdk5-PPAR-β, Ginsenoside Rg1-Aβ-Cdk5/PPARγ pathway, Cdk5/Calcineurin signaling, Cdk5/Drp1-mediated mitochondrial fission, GSK-3 β and TrkA/Cdk5, Cdk5/HIF-1 | (Mawuenyega et al., 2010; Palop and Mucke, 2010; Cheung and Ip, 2012; Jaiswal and Sharma, 2017; Lazarevic et al., 2017; Guo et al., 2018; Fang et al., 2019; Lapresa et al., 2019; Quan et al., 2019, 2020; Ribeiro Filho et al., 2019; Chao et al., 2020; Li et al., 2020a; Park et al., 2020; Ai et al., 2022) |
| Tau phosphorylation: Leukotriene/Cdk5, Cdk5/mitochondria and Golgi function, Cdk5/MARK4, Cdk5/RPS23RG1, miR-148a-3p/p35/PTEN signaling pathway, Quercetin-Ca2+- calpain-p25-Cdk5 pathway, miR-504–3p and CDK5 axis | (Mohamed et al., 2017; Shen et al., 2018; Wilkaniec et al., 2018; Giannopoulos et al., 2019; Saito et al., 2019; Xu et al., 2019; Huang et al., 2020; Zeng et al., 2021; Zhao et al., 2021; Tanaka et al., 2022) | ||
| Neurodegenerative diseases | Cdk5 inhibitor in AD: Cdk5/Mcl-1, Cdk5-/ALDH1A1, Cdk5/miR-125b, Nano-HO-JNK/Cdk5/GSK-3β, Kaixinsan/ GSK-3β and CDK5 | (Nikhil and Shah, 2017; Shukla et al., 2017; Nikhil et al., 2019; Zeb et al., 2019a, b; Zhuang et al., 2020a, b; Qu et al., 2021; Chen et al., 2022; Jiao et al., 2022) | |
| Parkinson’s disease | Cdk5/inflammation, Cdk5/immune hyperactivity, Cdk5/mitochondrial fission, Cdk5/degradation of ubiquitin ligases, Cdk5-Luteolin, phosphorylation induced SIRT2 nuclear translocation | (He et al., 2018; Wang et al., 2018; Park et al., 2019; Shukla et al., 2019; Cheng et al., 2020; Reudhabibadh et al., 2021; Yan et al., 2022) | |
| Huntington’s disease | P25/Cdk5, Cdk5-drp1, Cdk5/DARPP-32 | (Paoletti et al., 2008; Langhorne et al., 2011; Cherubini et al., 2015; Brito et al., 2019) | |
| Ischemia Stroke | Cdk5/Zinc chelator, Cdk5/neuregulin-1 β, Cdk5/TFP5, Cdk5/tat-Cdk5 CTM, Cdk5/ERK1/2 signaling pathway, Cdk5/inhibition of p53 dependent apoptosis, Cdk5/trkb-erk1/2-creb pathway, Cdk5/phosphorylation of drp1s616, miR-148b-3p via CDK5R1/SIRT1 | (Becerra-Calixto and Cardona-Gomez, 2017; Cui et al., 2017; Ji et al., 2017; Liu et al., 2017; Zhao et al., 2017; Munoz-Manco et al., 2018; Tuo et al., 2018; Zhang et al., 2018; Shin et al., 2019; Zhu et al., 2019; Chen et al., 2021, 2022) | |
| Cerebrovascular disease | Intracerebral Hemorrhage | Cdk5-ATM signalin pathway, Cdk5/P35, Cdk5- p75NTR | (Wu et al., 2016; Roufayel and Murshid, 2019; Zhou et al., 2019) |
| Neuropathic Pain | Cdk5/CREB, Cdk5/PPAR γ pathway, mir-196a-5p/Cdk5 axis, Cdk5/CRMP2, Cdk5-NR2A pathway, Cdk5/TRPA1 | (Li et al., 2014, 2020; Yang et al., 2014; Chernov et al., 2018; Sulak et al., 2018; Moutal et al., 2019; Zhong et al., 2019; Gomez et al., 2020a, 2021; Zhu et al., 2021) | |
| Epilepsy | Cdk5/mitochondrial fragmentation, Cdk5/neuroinflammation, Cdk5/endoplasmic reticulum stress, Cdk5/p38 MAPK mediated microglial response | (Tian et al., 2008, 2010; Li et al., 2016; Kim and Kang, 2017, 2018; Liu et al., 2017; Hiragi et al., 2018; Kim et al., 2019; Fan et al., 2020; Lee and Kim, 2021) | |
| Glioblastoma | Cdk5/PIKE-A, Cdk5/DRP1, miR-21/Cdk5, Cdk5/TP5, Cdk5/DYRK1A, Cdk5/AC1MYR2, Cdk5/TRIM59, OGT/CDK5/ACSS2 pathway | (Liu et al., 2008; Ren et al., 2015; Xie et al., 2015; Gonzalez-Vera et al., 2016; Sang et al., 2019; Peyressatre et al., 2020a, b; Tabouret et al., 2020; Chen et al., 2021; Zhou et al., 2021; Ciraku et al., 2022) | |
| Multiple sclerosis | Cdk5/oligodendrocytes, Cdk5/lymphocyte activation | (Pareek et al., 2010; Luo et al., 2016, 2018) | |
| Other neurological disorders | Cdk5/ERK1/2 pathway, Cdk5/caspase-3 pathway, Cdk5/CRMP-2, Cdk5/mitochondrial kinetic defects, Cdk5/Oxidative stress, Cdk5/endoplasmic reticulum stress, nestin-Cdk5-drp1 | (Lindqvist et al., 2017; Guo et al., 2018; Kamiki et al., 2018; Roach et al., 2018; Shi et al., 2018; Spurrier et al., 2018; Wang et al., 2018; Barrett et al., 2019; Chen et al., 2019; Liu et al., 2019; Sase et al., 2019; Li et al., 2020b; Rong et al., 2020; Shukla and Singh, 2020, 2022; Xia et al., 2020; Zhang et al., 2021; Daniels et al., 2022; Manglani and Dey, 2022; Takahashi et al., 2022b; Umfress et al., 2022; Zhou et al., 2022) |
Abbreviations: PPAR γ, Peroxisome proliferator-activated receptor gamma; APP, Aβ precursor protein; GSK-3 β, Glycogen Synthase Kinase-3; Drp, dynamin-related protein; MARK4, microtubule-affinityregulating kinase 4; TrkA, tropomyosin-relatedkinaseA; GSK-3 β, Glycogen synthase kinase; HIF-1, Hypoxia-inducible factor 1; RPS23RG1, The type Ib transmembrane protein; Mcl-1, myeloid-cell-leukemia-sequence-1; ALDH1A1, aldehyde dehydrogenase 1 family member A1; Fbxw7, F-box/WDrepeat-containing protein 7; TFP5, a modified truncated 24-aa peptide; DARPP-32, dopamine- and cyclic-AMP-regulated phosphoprotein of molecular weight 32,000; OGDR, The oxygen glucose deprivation reperfusion; MEF2D, myocyte enhancer factor 2D; p75 NTR, p75 neurotrophic factor receptor; ATM, Ataxia Telangiectasia Mutated; ERK1, Extracellular signal-regulated kinase 1; CREB, a transcription factor; TRPA1, transient receptor potential action channel 1; NR2A, N-methyl-D-aspartate receptor subunit 2A; NMDAR, N-methyl-D-aspartate receptor; MAPK, mitogen-activated protein kinases; TP5, a thymopentin; MTLE-HS, mesial temporal lobe epilepsy with hippocampal sclerosis; PIKE-A, Isoform A of phosphatidylinositol 3-kinase enhancer; DYRK1A, Dual-specificity tyrosine phosphorylation-regulated kinase 1A; ACSS2, acetate-dependent acetyl CoA synthetase 2; CRMP2, collapsin response mediator protein 2.