Identification of Common Molecular Signatures Shared between Alzheimer’s and Parkinson’s Diseases and Therapeutic Agents Exploration: An Integrated Genomics Approach

Abstract

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are two most prevalent age-related dementias that severely affect a large number of elderly people around the globe. Poor understanding of pathogenesis of these neurological diseases imposes challenge to discover therapeutic measures and effective diagnosis methods. In this study, a network-based approach was utilized to identify potential common molecular signatures and therapeutic agents for AD and PD. Protein-protein interaction analysis revealed NCK1, UBC, CDH1, CDC20, ACTB, PSMA7, PRPF8, RPL7, XRCC6 and HSP90AB1 as the best proteome signatures. Different regulatory transcriptional signatures i.e., YY1, NFKB1, BRCA1, TP53, GATA2, SREBF2, E2F1, FOXC1, RELA and NFIC and post-transcriptional signatures i.e., hsa-mir-186-5p, hsamir-92a-3p, hsa-mir-615-3p, hsa-let-7c-5p, hsa-mir-100-5p, hsa-mir-93-3p, hsa-mir-5681a, hsamir-484, hsa-mir-193b-3p and hsa-mir-16p-5p were identified from other interaction network. Drug-gene interaction study revealed possible therapeutic agents which may reverse the AD and PD condition. The scientific approach of this study should contribute to identify potential biomarkers, drug targets and therapeutic agents against AD and PD which should in turn advance the present efforts of scientists to secure effective diagnosis and therapeutic options. However, further in vivo and in vitro experiments might be required to validate the outcomes of this study.

Data Mining of Microarray Datasets in Translational Neuroscience

“…A data mining study that made use of blood datasets from MS patients found that the upregulation of miRNA hsa-miR-328-3p [ 128 ], hsa-miR-20a-5p [ 128 ], and miR-196 [ 129 ] occurred, as did the downregulation of miR-9 [ 129 ]. In AD, the dysregulation of miRNA has been identified in peripheral blood (upregulated: hsa-miR-186-5p [ 130 ]; downregulated: hsa-miR-125a-3p, hsa-miR-22-3p, hsa-miR-24-3p, hsa-miR-6131, and hsa-miR-125b-1-3p [ 131 ]) and in brain tissues (downregulated: hsa-miR-29c [ 132 ] and hsa-miR-26b-5p [ 133 ]). Another study found that the downregulation of miR-425 was implicated in AD pathogenesis, and a miR-425 deficient transgenic mouse was used to validate the results [ 134 ].…”

The Gut–Organ Axis within the Human Body: Gut Dysbiosis and the Role of Prebiotics

“…Parkinson's disease (PD) is the second most common degenerative disorder of the brain, affecting seven to ten million people worldwide [33]. PD is mainly characterised by multifactorial motor and non-motor symptoms, including resting tremor, muscular rigidity, slowness of movement, and gait abnormality, as well as cognitive disturbances, depression, mood deflection, sensory alternations, and sleep alternations [33,34].…”

“…Parkinson's disease (PD) is the second most common degenerative disorder of the brain, affecting seven to ten million people worldwide [33]. PD is mainly characterised by multifactorial motor and non-motor symptoms, including resting tremor, muscular rigidity, slowness of movement, and gait abnormality, as well as cognitive disturbances, depression, mood deflection, sensory alternations, and sleep alternations [33,34]. The principal pathology of PD is characterised by the loss of dopamine-producing neurons present in a specific region of the brain, known as the substantia nigra, accompanied by the accumulation of alfa-synuclein (alfa-syn) in the form of Lewy bodies and Lewy neurites, a condition known as synucleinopathy [35].…”

“…Complex genetic and environmental factors are involved in the etiology of PD; however, the cause of PD remains unknown. Gastrointestinal symptoms are observed in most PD patients, including hypersalivation, dysphagia, constipation, nausea, altered bowel habits, and defecatory dysfunction [33]. Several studies have demonstrated GM abnormalities in patients with PD [36][37][38].…”