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Widespread distribution of reticulon‐3 in various neurodegenerative diseases
Author(s) -
Heath Jonathon E.,
Siedlak Sandra L.,
Zhu Xiongwei,
Lee Hyounggon,
Thakur Akanksha,
Yan Riqiang,
Perry George,
Smith Mark A.,
Castellani Rudy J.
Publication year - 2010
Publication title -
neuropathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.701
H-Index - 61
eISSN - 1440-1789
pISSN - 0919-6544
DOI - 10.1111/j.1440-1789.2010.01107.x
Subject(s) - endoplasmic reticulum , neurite , neuropil , amyloid precursor protein , lewy body , biology , hippocampal formation , microbiology and biotechnology , neuroscience , pathology , alzheimer's disease , disease , medicine , parkinson's disease , central nervous system , biochemistry , in vitro
Reticulons are a group of membrane‐bound proteins involved in diverse cellular functions, and are suggested to act as inhibitors of β‐secretase enzyme 1 (BACE1) activity that cleaves amyloid precursor protein. Reticulons are known to accumulate in the dystrophic neurites of Alzheimer's disease (AD), and studies have suggested that alterations in reticulons, such as increased aggregation, impair BACE1 binding, increasing amyloid‐β production, and facilitating reticulon deposition in dystrophic neurites. To further characterize the cellular distribution of reticulon, we examined reticulon‐3 expression in cases of AD, Parkinson's disease, and diffuse Lewy body disease. A more widespread cellular distribution of reticulon‐3 was noted than in previous reports, including deposits in dystrophic neurites, neuropil threads, granulovacuolar degeneration, glial cells, morphologically normal neurons in both hippocampal pyramidal cell layer and cerebral neocortex, and specifically neurofibrillary tangles and Lewy bodies. These results are compatible with reticulon alterations as nonspecific downstream stress responses, consistent with its expression during periods of endoplasmic reticulum stress. This emphasizes the increasing recognition that much of the AD pathological spectrum represents a response to the disease rather than cause, and emphasizes the importance of examining upstream processes, such as oxidative stress, that have functional effects prior to the onset of structural alterations.