title: Complex network-driven view of genomic mechanisms underlying Parkinson's disease: analyses in dorsal motor vagal nucleus, locus coeruleus, and substantia nigra.
abstract: Parkinson's disease (PD)—classically characterized by severe loss of dopaminergic neurons in the substantia nigra pars compacta—has a caudal-rostral progression, beginning in the dorsal motor vagal nucleus and, in a less extent, in the olfactory system, progressing to the midbrain and eventually to the basal forebrain and the neocortex. About 90% of the cases are idiopathic. To study the molecular mechanisms involved in idiopathic PD we conducted a comparative study of transcriptional interaction networks in the dorsal motor vagal nucleus (VA), locus coeruleus (LC), and substantia nigra (SN) of idiopathic PD in Braak stages 4-5 (PD) and disease-free controls (CT) using postmortem samples. Gene coexpression networks (GCNs) for each brain region (patients and controls) were obtained to identify highly connected relevant genes (hubs) and densely interconnected gene sets (modules). GCN analyses showed differences in topology and module composition between CT and PD networks for each anatomic region. In CT networks, VA, LC, and SN hub modules are predominantly associated with neuroprotection and homeostasis in the ageing brain, whereas in the patient's group, for the three brain regions, hub modules are mostly related to stress response and neuron survival/degeneration mechanisms.
authors.affiliation: Department of Pediatrics, Faculdade de Medicina da USP (FMUSP), Avenida Dr. Enéas Carvalho Aguiar 647, 5 Andar, 05403-900 São Paulo, SP, Brazil.
authors.forename: Beatriz Raposo
authors.initials: BR
authors.lastname: Corradini
authors.affiliation: Department of Pediatrics, Faculdade de Medicina da USP (FMUSP), Avenida Dr. Enéas Carvalho Aguiar 647, 5 Andar, 05403-900 São Paulo, SP, Brazil.
authors.forename: Priscila
authors.identifier: 0000-0001-7375-1700
authors.initials: P
authors.lastname: Iamashita
authors.affiliation: Brazilian Aging Brain Study Group (BEHEEC), LIM 22, FMUSP, 01246-903 São Paulo, SP, Brazil ; Hospital Israelita Albert Einstein, 05652-900 São Paulo, SP, Brazil.
authors.forename: Edilaine
authors.initials: E
authors.lastname: Tampellini
authors.affiliation: Hospital Israelita Albert Einstein, 05652-900 São Paulo, SP, Brazil ; Division of Geriatrics, FMUSP, 01246-903 São Paulo, SP, Brazil.
authors.forename: José Marcelo
authors.initials: JM
authors.lastname: Farfel
authors.affiliation: Brazilian Aging Brain Study Group (BEHEEC), LIM 22, FMUSP, 01246-903 São Paulo, SP, Brazil ; Department of Pathology, FMUSP, 01246-903 São Paulo, SP, Brazil ; Department of Neurology and Pathology, University of California, San Francisco, CA 94143, USA.
authors.forename: Lea Tenenholz
authors.initials: LT
authors.lastname: Grinberg
authors.affiliation: Department of Pediatrics, Faculdade de Medicina da USP (FMUSP), Avenida Dr. Enéas Carvalho Aguiar 647, 5 Andar, 05403-900 São Paulo, SP, Brazil.
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Moreira-Filho
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000473:pathology; D017209:Apoptosis / Q000235:genetics; D001344:Autopsy; D059290:Dopaminergic Neurons / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D053263:Gene Regulatory Networks / Q000235:genetics; D023281:Genomics; D006801:Humans; D008125:Locus Coeruleus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000235:genetics / Q000473:pathology; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology; D013378:Substantia Nigra / Q000378:metabolism* / Q000473:pathology