Genetic and Molecular Bases of Neurodegeneration

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Human Genomics and Genetic Diseases".

Deadline for manuscript submissions: 15 July 2024 | Viewed by 949

Special Issue Editor


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Guest Editor
Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA
Interests: neurodegeneration; aging; genetics; genomics; somatic mutations; duplex sequencing

Special Issue Information

Dear Colleagues,

Advances in sequencing and omics data are providing an unprecedented opportunity to understand what causes and contributes to neurodegeneration. Notable breakthrough discoveries of familial inherited mutations and associated genetic risk factors, together with the arduous work carried out regarding their functional consequences, are slowly clarifying the events underlying the most common forms of neurodegeneration, such as Alzheimer’s disease, bringing promising insight into other less common neurodegenerative disorders. To advance our understanding of neurodegeneration, not only are more studies needed on how known genetic factors contribute to the molecular events that end in neuronal damage and loss at the core of the neurodegenerative process, but also interdisciplinary approaches able to address its complexity and explore the interplay between known and novel molecular pathways. With continuous technological developments becoming more available to the average laboratory, all our previous hypotheses of the molecular mechanisms involved in neurodegeneration can now be put to the test while creating an avenue for discovery that promises to advance the field towards preventing, delaying, or treating neurodegenerative disorders.

Dr. Monica Sanchez-Contreras
Guest Editor

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Keywords

  • familial mutations
  • sporadic
  • risk factors
  • protein aggregation
  • proteinopathies
  • neuronal loss
  • mitochondrial dysfunction
  • progression
  • onset
  • aging

Published Papers (1 paper)

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11 pages, 5373 KiB  
Brief Report
Olfactory Receptor OR2K2 Expression in Human Choroid Plexus as a Potential Marker in Early Sporadic Alzheimer’s Disease
by Victoria Cunha Alves, Joana Figueiro-Silva, Ramon Trullas, Isidre Ferrer and Eva Carro
Genes 2024, 15(3), 385; https://doi.org/10.3390/genes15030385 - 21 Mar 2024
Viewed by 808
Abstract
Epithelial cells comprising the choroid plexus (CP) form a crucial barrier between the blood and the cerebrospinal fluid, thereby assuming a central position in brain homeostasis and signaling. Mounting evidence suggests that the impairment of CP function may be a significant contributor to [...] Read more.
Epithelial cells comprising the choroid plexus (CP) form a crucial barrier between the blood and the cerebrospinal fluid, thereby assuming a central position in brain homeostasis and signaling. Mounting evidence suggests that the impairment of CP function may be a significant contributor to Alzheimer’s disease (AD) pathogenesis. CP function relies on the expression of specific receptors, and the potential involvement of olfactory receptors (ORs) and taste receptors (TASRs) in chemical surveillance within the CP is being investigated. Previous studies have implicated ORs and TASRs in neurodegenerative disorders like AD, although the direct evidence of their expression in the human CP remains to be established. In this study, we conducted a transcriptomic analysis encompassing eleven ORs and TASRs in the CP, comparing samples from healthy age-matched controls to those from patients with AD spanning Braak stages I to VI. Among these receptors, a striking finding emerged—OR2K2 exhibited robust expression, with a statistically significant upregulation noted at Braak stage I. Surprisingly, at the protein level, OR2K2 showed a significant decrease in both Braak stage I and VI. Additionally, we identified CP epithelial cells as the source of OR2K2 expression, where it colocalized with autophagy markers LC3 and p62. We postulate that OR2K2 could be subjected to degradation by autophagy in the early stages of AD, triggering a compensatory mechanism that leads to increased OR2K2 mRNA transcription. This study uncovers a potential role for OR2K2 in AD pathogenesis, offering a novel perspective on the intricate dynamics at play in this neurodegenerative disorder. Full article
(This article belongs to the Special Issue Genetic and Molecular Bases of Neurodegeneration)
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