Evaluation of the Common Molecular Basis in Alzheimer’s and Parkinson’s Diseases

Abstract

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common neurodegenerative disorders related to aging. Though several risk factors are shared between these two diseases, the exact relationship between them is still unknown. In this paper, we analyzed how these two diseases relate to each other from the genomic, epigenomic, and transcriptomic viewpoints. Using an extensive literature mining, we first accumulated the list of genes from major genome-wide association (GWAS) studies. Based on these GWAS studies, we observed that only one gene (HLA-DRB5) was shared between AD and PD. A subsequent literature search identified a few other genes involved in these two diseases, among which SIRT1 seemed to be the most prominent one. While we listed all the miRNAs that have been previously reported for AD and PD separately, we found only 15 different miRNAs that were reported in both diseases. In order to get better insights, we predicted the gene co-expression network for both AD and PD using network analysis algorithms applied to two GEO datasets. The network analysis revealed six clusters of genes related to AD and four clusters of genes related to PD; however, there was very low functional similarity between these clusters, pointing to insignificant similarity between AD and PD even at the level of affected biological processes. Finally, we postulated the putative epigenetic regulator modules that are common to AD and PD.

NaSH increases SIRT1 activity and autophagy flux through sulfhydration to protect SH-SY5Y cells induced by MPP~+

“…H 2 S has been widely considered as a toxic gas in the scientific community for over 300 y, but understanding of this small molecule has changed since H 2 S is found to involve in the physiological and pathological mechanism of the brain [20]. SIRT1 was suggested to suppress the synuclein aggregate formation in PD and it was also correlated with H 2 S in neuronal senescence and diabetes [14,15,21]. Herein, this study aims to investigate the roles of H 2 S and SIRT1 in PD, and drew a conclusion that H 2 S ameliorated SIRT1 activity through acceleration of SIRT1 sulfhydration to increase the autophagy flux and attenuate damage of SH-SY5Y cells induced by MPP~+.…”

Environment and Gene Association With Obesity and Their Impact on Neurodegenerative and Neurodevelopmental Diseases

“…Some of the genes mentioned below are APOE and TREM2 associated with AD; CD38 variants with AD and PD; and SYT4 with PD ( Chang et al, 2018 ; Jansen et al, 2019 ). In addition, genetic studies found the association of SIRT1 with PD and AD ( Zhang A. et al, 2012 ; Rana et al, 2019 ) and with SCZ ( Kishi et al, 2011 ). A similar strategy to select the genes associated with NDvD as SCZ and ASD.…”

“…Moreover, low levels of SIRT1 are present in NDgD as AD and PD ( Lutz et al, 2014 ; Singh et al, 2017 ). In addition, genetic studies found the association of SIRT1 with PD and AD ( Zhang A. et al, 2012 ; Rana et al, 2019 ) and with SCZ ( Kishi et al, 2011 ).…”

Editorial to the Special Issue “Lipidomics and Neurodegenerative Diseases”

“…In the second review [ 12 ], Rana et al analyzed how AD and PD could relate to each other from the genomic, epigenomic, and transcriptomic viewpoints since their relationship is still unidentified. AD is clinically characterized by a steady loss of memory and impairment of other cognitive functions such as communication, language inability, advanced visual processing, and movement [ 13 ].…”

“…While the mutual pathological overlap may be linked to genes, mitochondrial dysfunction, neuroinflammation, tau protein, and α-synuclein protein [ 15 ], common risk factors are signified by oxidative stress, insufficiency of vitamin D, and aging [ 16 ]. In the present review [ 12 ], Rana et al first accumulated a list of genes from major genome-wide association (GWAS) studies by recurring to extensive literature mining. As a result of GWAS studies, the authors recovered only one gene (i.e., HLA-DRB5) shared between AD and PD that has been reported earlier several times for AD and PD, exhibiting a strong relationship with the CNS.…”