title: Does the oxysterol 27-hydroxycholesterol underlie Alzheimer's disease-Parkinson's disease overlap?
abstract: Alzheimer's disease (AD), the most common form of dementia, is characterized histopathologically by the deposition of β-amyloid (Aβ) plaques and neurofibrillary tangles-containing hyperphosphorylated tau protein in the brain. Parkinson's disease (PD), the most common movement disorder, is characterized by the aggregation of α-synuclein protein in Lewy body inclusions and the death of dopaminergic neurons in the substantia nigra. Based on their pathological signatures, AD and PD can be considered as two different disease entities. However, a subpopulation of PD patients also exhibit Aβ plaques, and AD patients exhibit α-synuclein aggregates. This overlap between PD and AD suggests that common pathological pathways exist for the two diseases. Identification of factors and cellular mechanisms by which these factors can trigger pathological hallmarks for AD/PD overlap may help in designing disease-modifying therapies that can reverse or stop the progression of AD and PD. For the last decade, work in our laboratory has shown that fluctuations in the levels of cholesterol oxidation products (oxysterols) may correlate with the onset of AD and PD. In this review, we will provide results from our laboratory and data from literature that converge to strongly suggest the involvement of cholesterol and cholesterol oxidation products in the pathogenesis of AD and PD. We will specifically delineate the role of and the underlying mechanisms by which increased levels of the oxysterol 27-hydroxycholesterol contribute to the pathogenesis of AD, PD, and AD/PD overlap.
authors.affiliation: Department of Basic Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202, United States.
authors.forename: Gurdeep
authors.initials: G
authors.lastname: Marwarha
authors.affiliation: Department of Basic Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202, United States. Electronic address: othman.ghribi@med.und.edu.
authors.forename: Othman
authors.initials: O
authors.lastname: Ghribi
mesh_terms: D000544:Alzheimer Disease / Q000097:blood / Q000209:etiology*; D000818:Animals; D001921:Brain / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000494:pharmacology; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D006888:Hydroxycholesterols / Q000378:metabolism*; D050356:Lipid Metabolism / Q000502:physiology; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D010300:Parkinson Disease / Q000097:blood / Q000209:etiology*; D058225:Plaque, Amyloid / Q000378:metabolism; D011817:Rabbits; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D002791:Cholesterol, Dietary; D006888:Hydroxycholesterols; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D051844:alpha-Synuclein; C076996:27-hydroxycholesterol
keywords: Alpha synuclein; Alzheimer's disease; Endoplasmic reticulum stress; Oxysterols; Parkinson's disease