title: Looking beyond the brain to improve the pathogenic understanding of Parkinson's disease: implications of whole transcriptome profiling of Patients' skin.
abstract: BACKGROUND
  Parkinson'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.
  
  
  METHODS
  To 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.
  
  
  RESULTS
  This 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.
  
  
  CONCLUSIONS
  These 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.
authors.affiliation: North-Estonian Medical Centre, Sütiste Rd.19, Tallinn, 13419, Estonia. anu.planken@regionaalhaigla.ee.
authors.forename: Anu
authors.identifier: http://orcid.org/0000-0003-4553-1852
authors.initials: A
authors.lastname: Planken
authors.affiliation: Faculty of Medicine, University of Tartu, Tartu, Estonia.
authors.forename: Lille
authors.initials: L
authors.lastname: Kurvits
authors.affiliation: Institute of Pathophysiology, University of Tartu, Tartu, Estonia.
authors.forename: Ene
authors.initials: E
authors.lastname: Reimann
authors.affiliation: Department of Neurology and Neurosurgery, University of Tartu, Tartu, Estonia.
authors.forename: Liis
authors.initials: L
authors.lastname: Kadastik-Eerme
authors.affiliation: Department of Dermatology, University of Tartu, Tartu, Estonia.|Dermatology Clinic, Tartu University Hospital, Tartu, Estonia.
authors.forename: Külli
authors.initials: K
authors.lastname: Kingo
authors.affiliation: Institute of Pathophysiology, University of Tartu, Tartu, Estonia.
authors.forename: Sulev
authors.initials: S
authors.lastname: Kõks
authors.affiliation: Department of Neurology and Neurosurgery, University of Tartu, Tartu, Estonia.
authors.forename: Pille
authors.initials: P
authors.lastname: Taba
mesh_terms: D000368:Aged; D001921:Brain / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D008297:Male; D010300:Parkinson Disease / Q000235:genetics*
keywords: Gene expression; High-throughput RNA sequencing; Neurodegeneration; Parkinson’s Disease; Skin-brain crosstalk