Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/127473
Title: Dementia with lewy bodies: molecular pathology in the frontal cortex in typical and rapidly progressive forms
Author: Garcia Esparcia, Paula
López González, Irene
Grau-Rivera, Oriol
García Garrido, María Francisca
Koneti, Anusha
Llorens Torres, Franc
Zafar, Saima
Carmona Murillo, Margarita
Río Fernández, José Antonio del
Zerr, Inga
Gelpi, Ellen
Ferrer, Isidro (Ferrer Abizanda)
Keywords: Demència amb cossos de Lewy
Malaltia d'Alzheimer
Mitocondris
Síntesi proteica
Inflamació
Lewy body dementia
Alzheimer's disease
Mitochondria
Protein synthesis
Inflammation
Issue Date: 13-Mar-2017
Publisher: Frontiers Media
Abstract: Objectives: the goal of this study was to assess mitochondrial function, energy, and purine metabolism, protein synthesis machinery from the nucleolus to the ribosome, inflammation, and expression of newly identified ectopic olfactory receptors (ORs) and taste receptors (TASRs) in the frontal cortex of typical cases of dementia with Lewy bodies (DLB) and cases with rapid clinical course (rpDLB: 2 years or less) compared with middle-aged non-affected individuals, in order to learn about the biochemical abnormalities underlying Lewy body pathology. Methods: real-time quantitative PCR, mitochondrial enzymatic assays, and analysis of β-amyloid, tau, and synuclein species were used. Results: the main alterations in DLB and rpDLB, which are more marked in the rapidly progressive forms, include (i) deregulated expression of several mRNAs and proteins of mitochondrial subunits, and reduced activity of complexes I, II, III, and IV of the mitochondrial respiratory chain; (ii) reduced expression of selected molecules involved in energy metabolism and increased expression of enzymes involved in purine metabolism; (iii) abnormal expression of nucleolar proteins, rRNA18S, genes encoding ribosomal proteins, and initiation factors of the transcription at the ribosome; (iv) discrete inflammation; and (v) marked deregulation of brain ORs and TASRs, respectively. Severe mitochondrial dysfunction involving activity of four complexes, minimal inflammatory responses, and dramatic altered expression of ORs and TASRs discriminate DLB from Alzheimer's disease. Altered solubility and aggregation of α-synuclein, increased β-amyloid bound to membranes, and absence of soluble tau oligomers are common in DLB and rpDLB. Low levels of soluble β-amyloid are found in DLB. However, increased soluble β-amyloid 1-40 and β-amyloid 1-42, and increased TNFα mRNA and protein expression, distinguish rpDLB. Conclusion: molecular alterations in frontal cortex in DLB involve key biochemical pathways such as mitochondria and energy metabolism, protein synthesis, purine metabolism, among others and are accompanied by discrete innate inflammatory response.
Note: Reproducció del document publicat a: https://doi.org/10.3389/fneur.2017.00089
It is part of: Frontiers In Neurology, 2017, vol. 8, p. 89
URI: http://hdl.handle.net/2445/127473
Related resource: https://doi.org/10.3389/fneur.2017.00089
ISSN: 1664-2295
Appears in Collections:Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)
Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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