Abstract
BackgroundParkinson’s Disease is a progressive neurodegenerative disease, characterized by symptoms of motor impairment, resulting from the loss of dopaminergic neurons in the midbrain, however non-neuronal symptoms are also common. Although great advances have been made in the pathogenic understanding of Parkinson’s Disease in the nervous system, little is known about the molecular alterations occurring in other non-neuronal organ systems. In addition, a higher rate of melanoma and non-melanoma skin cancer has been observed in the Parkinson’s Disease population, indicating crosstalk between these diseases.MethodsTo understand the molecular pathogenesis and gene expression alterations of Parkinson’s Disease in peripheral tissues, and in order to explore the possible link between skin cancer and neurodegeneration, whole transcriptomic profiling of patients’ skin was performed. Skin biopsies from 12 patients and matched controls were collected, and processed with high-throughput RNA-sequencing analysis.ResultsThis analysis resulted in a large collection of over 1000 differentially expressed genes, among which clear biological and functional networks could be distinguished. The central functional processes altered in patients skin can be grouped into six broad categories: impaired cellular metabolism and mitochondrial dysfunction, defective protein metabolism, disturbed skin homeostasis, dysfunctional nuclear processes, altered signalling and tumour pathways, as well as disordered immune regulation.ConclusionsThese results demonstrate that the molecular alterations leading to neurodegeneration in the CNS are systemic and manifest also in peripheral tissues, thereby indicating the presence of “skin-brain” crosstalk in Parkinson’s Disease. In addition, the extensive homeostatic imbalance and basal stress can lead to increased susceptibility to external and internal mutagenic hazards in these patients, and thus provide a possible molecular link for the crosstalk between skin cancer and Parkinson’s Disease.
Highlights
Parkinson’s Disease is a progressive neurodegenerative disease, characterized by symptoms of motor impairment, resulting from the loss of dopaminergic neurons in the midbrain, non-neuronal symptoms are common
The Ingenuity Pathway Analysis resulted in 10 major functional networks to be influenced by Parkinson’s disease (PD) including (Table 1.): 1) gene expression, protein synthesis, dermatological disease and conditions; 2) dermatological diseases and conditions, immunological disease and inflammatory disease (35/23); 3) cellular assembly and organization, behaviour, cell signalling (34/23); 4) cancer, immunological disease, cellular development (33/22); 5) connective tissue disorder, dermatological
Our study revealed a coordinated suppression of parallel pathways of the cornification and desquamation processes, highlighted by the suppression of the epidermal differentiation complex (EDC), which contains 57 genes crucial for the differentiation process located within a tight cluster on chromosome 1q21 (20 genes of EDC supressed) and ephrin A1, which is a central regulator of epidermal growth, located in close proximity to the EDC on chromosome 1q arm
Summary
Parkinson’s Disease is a progressive neurodegenerative disease, characterized by symptoms of motor impairment, resulting from the loss of dopaminergic neurons in the midbrain, non-neuronal symptoms are common. Great advances have been made in the pathogenic understanding of Parkinson’s Disease in the nervous system, little is known about the molecular alterations occurring in other non-neuronal organ systems. Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by symptoms of resting tremor, rigidity, bradykinesia and postural instability. The motor symptoms of PD are considered to result from the loss of substantia nigra dopaminergic neurons, Planken et al BMC Neurology (2017) 17:6 but rather as a multisystem progressive disorder [3]. Numerous studies have investigated the pathogenic processes occurring in the nervous system, the reflection of disease pathology in the peripheral tissues, has been poorly characterized. Due to lack of diagnostic and prognostic biomarkers a definitive diagnosis for PD can only be performed post-mortem, information on PD pathogenesis, with possible outlook on novel biomarkers or disease-modifying therapy, is of great value
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