中国神经再生研究(英文版) ›› 2025, Vol. 20 ›› Issue (7): 1997-1998.doi: 10.4103/NRR.NRR-D-24-00334

• 观点:退行性病与再生 • 上一篇    下一篇

使用嗅觉组学图谱的数据驱动药物重新定位:神经退行性变的挑战和前景

  

  • 出版日期:2025-07-15 发布日期:2024-11-26

Data-driven drug repositioning using olfactory omics profiles: challenges and perspectives in neurodegeneration

Paz Cartas-Cejudo, Adriana Cortés, Mercedes Lachén-Montes, Elena Anaya-Cubero, Joaquín Fernández-Irigoyen, Enrique Santamaría*   

  1. Clinical Neuroproteomics Unit, Proteomics Platform, Navarrabiomed, Hospitalario Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
  • Online:2025-07-15 Published:2024-11-26
  • Contact: Enrique Santamaría, PhD, esantamma@navarra.es.
  • Supported by:
    This work was funded by grants from the Spanish Ministry of Science, Innovation and Universities (Ref. PID2019-110356RB-I00/ AEI/10.13039/501100011033) to JFI and ES and the Department of Economic and Business Development from Government of Navarra (Ref. 0011-1411-2023-000028 to ES). PCC was supported by a predoctoral fellowship from the Public University of Navarra (UPNA). MLM was supported by a postdoctoral fellowship from Miguel Servet Foundation-Navarrabiomed. EAC was supported by “Programa MRR Investigo 2023” in the framework of the European Union recovery and resilience facility.

摘要: https://orcid.org/0000-0001-8046-8102 (Enrique Santamaría)

Abstract: Neurodegenerative diseases are characterized by progressive degeneration and loss of neuronal function in the central nervous system. These diseases are often characterized as proteinopathies, which are disorders primarily driven by the aggregation or misfolding of specific amyloid proteins within cells, leading to their dysfunction and eventual death. Despite the gainof-function hypothesis related to the aggregation of these proteins, recently, an alternative hypothesis regarding the loss-of-function of the soluble monomeric proteins during the process of aggregation into amyloids is gaining currency. This last event is called proteinopenia and refers to conditions characterized by a deficiency or decrease in the levels of specific soluble proteins in the body (Ezzat et al., 2023). It has been demonstrated that levels of soluble proteins involved in neurodegenerative diseases are decreased. In Alzheimer’s disease (AD), the brain accumulates abnormal protein aggregates forming amyloid-β (Aβ) plaques and Tau tangles. Although not all Aβ-positive individuals develop dementia, there is a 1:1 relationship between low soluble Aβ42 and dementia (Andreasen et al., 2001). When Aβ42 monomers transition into amyloid, both the Aβ42 pool and its neurotrophic properties diminish, consequently producing more harm to the brain than the accumulation of insoluble Aβ (Espay et al., 2023). Hence, the pathology signifies the loss of functional proteins rather than their conversion into a prion-like agent. Given this shift in the field, new ways to discover therapies are needed. For that, novel drug repositioning approaches are emerging with the aim to reverse more extensive metabolic imbalance instead of current approaches exclusively targeting protein toxic aggregates.