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Current neuropharmacology
2023;21 (1): 31-53.

Biological Mechanism-based Neurology and Psychiatry: A BACE1/2 and Downstream Pathway Model.

Harald Hampel, Giuseppe Caruso, Robert Nisticò, Gaia Piccioni, Nicola B Mercuri, Filippo Sean Giorgi, Fabio Ferrarelli, Pablo Lemercier, Filippo Caraci, Simone Lista, Andrea Vergallo
Author Information
  1. Harald Hampel: Sorbonne University, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, Paris, France.
  2. Giuseppe Caruso: Oasi Research Institute-IRCCS, Troina, Italy.
  3. Robert Nisticò: Laboratory of Pharmacology of Synaptic Plasticity, EBRI Rita Levi-Montalcini Foundation, Rome, Italy.
  4. Gaia Piccioni: Laboratory of Pharmacology of Synaptic Plasticity, EBRI Rita Levi-Montalcini Foundation, Rome, Italy.
  5. Nicola B Mercuri: Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy.
  6. Filippo Sean Giorgi: Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Pisa, Italy.
  7. Fabio Ferrarelli: Department of Psychiatry, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA.
  8. Pablo Lemercier: Sorbonne University, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, Paris, France.
  9. Filippo Caraci: Oasi Research Institute-IRCCS, Troina, Italy.
  10. Simone Lista: Sorbonne University, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, Paris, France.
  11. Andrea Vergallo: Sorbonne University, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, Paris, France.
PMID: 34852743 DOI: 10.2174/1570159X19666211201095701

Abstract

In oncology, comprehensive omics and functional enrichment studies have led to an extensive profiling of (epi)genetic and neurobiological alterations that can be mapped onto a single tumor's clinical phenotype and divergent clinical phenotypes expressing common pathophysiological pathways. Consequently, molecular pathway-based therapeutic interventions for different cancer typologies, namely tumor type- and site-agnostic treatments, have been developed, encouraging the real-world implementation of a paradigm shift in medicine. Given the breakthrough nature of the new-generation translational research and drug development in oncology, there is an increasing rationale to transfertilize this blueprint to other medical fields, including psychiatry and neurology. In order to illustrate the emerging paradigm shift in neuroscience, we provide a state-of-the-art review of translational studies on the β-site amyloid precursor protein cleaving enzyme (BACE) and its most studied downstream effector, neuregulin, which are molecular orchestrators of distinct biological pathways involved in several neurological and psychiatric diseases. This body of data aligns with the evidence of a shared genetic/biological architecture among Alzheimer's disease, schizoaffective disorder, and autism spectrum disorders. To facilitate a forward-looking discussion about a potential first step towards the adoption of biological pathway-based, clinical symptom-agnostic, categorization models in clinical neurology and psychiatry for precision medicine solutions, we engage in a speculative intellectual exercise gravitating around BACE-related science, which is used as a paradigmatic case here. We draw a perspective whereby pathway-based therapeutic strategies could be catalyzed by highthroughput techniques embedded in systems-scaled biology, neuroscience, and pharmacology approaches that will help overcome the constraints of traditional descriptive clinical symptom and syndrome-focused constructs in neurology and psychiatry.

Keywords

neurology precision medicine psychiatry systems biology systems pharmacology β-site amyloid precursor protein cleaving enzyme (BACE)

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MeSH Term

Humans
Amyloid Precursor Protein Secretases
Aspartic Acid Endopeptidases
Alzheimer Disease
Neurology
Amyloid beta-Protein Precursor
Psychiatry

Chemicals

Amyloid Precursor Protein Secretases
Aspartic Acid Endopeptidases
Amyloid beta-Protein Precursor
BACE1 protein, human
Journal Article
Article has an altmetric score of 10

Word Cloud

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