Gene Expression Analysis Reveals Genes Common to Cerebral Malaria and Neurodegenerative Disorders

J Infect Dis. 2017 Sep 15;216(6):771-775. doi: 10.1093/infdis/jix359.

Abstract

Cerebral malaria, a reversible encephalopathy affecting young children, is a medical emergency requiring urgent clinical assessment and treatment. We performed a whole-transcriptomic analysis of blood samples from Malian children with cerebral or uncomplicated malaria. We focused on transcripts from pathways for which dysfunction has been associated with neurodegenerative disorders. We found that SNCA, SIAH2, UBB, HSPA1A, TUBB2A, and PINK1 were upregulated (fold-increases, ≥2.6), whereas UBD and PSMC5 were downregulated (fold-decreases, ≤4.39) in children with cerebral malaria, compared with those with uncomplicated malaria. These findings provide the first evidence for pathogenic mechanisms common to human cerebral malaria and neurodegenerative disorders.

Keywords: PBMCs; cerebral malaria; common pathways; expression; human; mRNA; neurodegenerative disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Child
  • Child, Preschool
  • Down-Regulation
  • Female
  • Gene Expression Profiling
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism
  • Humans
  • LIM Domain Proteins / genetics
  • LIM Domain Proteins / metabolism
  • Leukocytes, Mononuclear / parasitology
  • Malaria, Cerebral / diagnosis
  • Malaria, Cerebral / genetics*
  • Malaria, Falciparum / diagnosis
  • Malaria, Falciparum / genetics*
  • Male
  • Neurodegenerative Diseases / diagnosis
  • Neurodegenerative Diseases / genetics*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Plasmodium falciparum
  • Prospective Studies
  • Proteasome Endopeptidase Complex
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Reproducibility of Results
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Tubulin / genetics
  • Tubulin / metabolism
  • Ubiquitin / genetics
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitins / genetics
  • Ubiquitins / metabolism
  • Up-Regulation
  • alpha-Synuclein / genetics
  • alpha-Synuclein / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • HSP70 Heat-Shock Proteins
  • HSPA1A protein, human
  • LIM Domain Proteins
  • Nuclear Proteins
  • PSMC5 protein, human
  • SNCA protein, human
  • TUBB2B protein, human
  • Transcription Factors
  • Tubulin
  • UBB protein, human
  • UBD protein, human
  • Ubiquitin
  • Ubiquitins
  • alpha-Synuclein
  • Ubiquitin-Protein Ligases
  • seven in absentia proteins
  • Protein Kinases
  • PTEN-induced putative kinase
  • Proteasome Endopeptidase Complex
  • ATPases Associated with Diverse Cellular Activities