Cell Cycle Deficits in Neurodegenerative Disorders: Uncovering Molecular Mechanisms to Drive Innovative Therapeutic Development

Joseph Chitra, Mangani Abubakar Siddiq, Gupta Veer, Chitranshi Nitin, Shen Ting, Dheer Yogita, KB Devaraj, Mirzaei Mehdi, You Yuyi, Graham Stuart L, Gupta Vivek

Table 1 Cell cycle modulatory proteins/genes identified in Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and ophthalmic neurodegenerative disorders such as glaucoma, age related macular degeneration (AMD) and diabetic retinopathies are listed along with the tissues examined.

Diseases Gene Region Cell cycle phase Refs Alzheimer's disease CDK1/Cdc2, Cyclin B1 Neurons with neurofibrillary tangle s (IHC) G0-G1, G2/M [108] Cdk5 Whole brain lysate (WB) S [109] p25/CDK5 Neuro fibrillary tangle bearing neurons (WB, IHC) G1/S [110] cyclin B1, cyclin D, CDK4, PCNA Hippocampus, subiculum, locus coeruleus, dorsal raphe, inferotemporal cortex, cerebellum G1/S, M [111] Cyclin D1, cyclin E, Cyclin A pRb Cortical neurons exposed to β amyloid G1/S [112] CDK2, CDK4, CDK6, cyclin B, and cyclin D Peripheral lymphocytes (WB) G1/S, M [113] CDK4, p16 Hippocampus (IHC) G1 [114] P25, p35 Frontal cortex, inferior parietal cortex and hippocampus (WB) G1/S [115] CDC25A neurofibrillary tangles and senile plaque bearing neurons Hippocampus (WB, IHC) G1/S [116] Cyclin D, PCNA, Cyclin B1 Hippocampus (IHC) G1/S, M [108] Cdc2/Cyclin B1, CyclinD1, CDK4, pRb PCNA Hemibrain homogenates G1/S, M [117] Hippocampus (WB, IHC) G1/S BAX Senile plaques Hippocampus (IHC) [118] P53 superior temporal gyrus (WB) G1 [119] Rb neurofibrillary tangles and senile plaque bearing neurons (IHC) Hippocampus G1/S [120] Glaucoma & other retinal disorders Gadd45a and Ei24(p53 family) Retina (qPCR and WB) [121] Cyclin D1 Optic nerve head (ONH) (Microarray) G1 [122] CDKN2A & CDKN2B Retina (RT-PCR) G1 [123] Cyclin B1 RPE cells (WB) G2/M [124] p53, p21 RPE cells (WB) G1 [125] p16 Primary RPE cells (WB) G1 [126] CDKN1 RPE cells (WB) G1 [127] NUCKS1 peripheral human retina (PR) and peripheral RPE-Choroid-Scleral (PRCS) tissues (RNA-Seq) M [128] Cyclin D Macular cells (qRT PCR) G1 [129] Bax Retina (WB & IF) G1 [130] p27Kip1 Retina (IHC) G1 [131] p53 Retinal pericytes (WB) G1 [132] Amyotrophic lateral sclerosis E2f, cyclin D1, CDK4, pRb lumbar spinal cord and pre-/postcentral gyrus (IHC, WB) G1 [133] Bax, caspase 3, caspase 8, p53, ppRb lumbar spinal cord (IHC, IF, WB) G1 [134] P53 Spinal cord, motor cortex (IHC, WB) G1 [135] CDK5 Spinal cord (IHC, WB) G1/S [136] CDK4, CDK5, CDK6, cyclin D1 Spinal cord (IHC) G1 [137] Parkinson's disease Rb SN nuclei, Frontal cortex and hippocampus (IHC) G1/S [138] PCNA, E2F, Dopaminergic neurons in SN (IHC, IF) G1/S [139] PCNA, Dopaminergic neurons in SN(IF) G1/S [140] cyclin D, cyclin A, cyclin E and cyclin B IF of embryonic rat mid brain neurons G1/S, G2/M CDK5, CDK2 Dopaminergic neurons in SN (IHC, WB, kinase assay) in MTP treated mice G1/S p53 caudate nucleus (WB) in human PD brain G1 [141] p53 Dopaminergic cells (IF, WB) in vitro (6-hydroxydopamine) and mouse model (PQ/MB) Whole brain lysates (WB) in human PD brains G1 [142, 143]