Widespread distribution of reticulon-3 in various neurodegenerative diseases

Jonathon E. Heath, Sandra L. Siedlak, Xiongwei Zhu, Hyoung Gon Lee, Akanksha Thakur, Riqiang Yan, George Perry, Mark A. Smith, Rudy J. Castellani*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)574-579
Number of pages6
JournalNeuropathology
Volume30
Issue number6
DOIs
StatePublished - Dec 2010
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Amyloid
  • Diffuse Lewy body disease
  • Dystrophic neurite
  • Oxidative stress
  • Parkinson's disease
  • Reticulon

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology

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