Increased neuronal Rab5 immunoreactive endosomes do not colocalize with TDP-43 in motor neuron disease

Radoslav Matej, Gergö Botond, Lajos László, Natasa Kopitar-Jerala, Robert Rusina, Herbert Budka, Gabor G. Kovacs

Research output: Contribution to journalArticle

9 Citations (Scopus)


Sporadic motor neuron disease (MND) is characterized by progressive degeneration of motor neurons and intraneuronal cytoplasmic translocation and deposition of the nuclear protein TDP-43. There is a paucity of data on the subcellular mechanisms of the nuclear-cytoplasmic trafficking of TDP-43, particularly about the precise role of the endosomal-lysosomal system (ELS). In the present study, using a neuron-specific morphometric approach, we examined the expression of the early endosomal marker Rab5 and lysosomal cathepsins B, D, F, and L as well as PAS-stained structures in the anterior horn cells in 11 individuals affected by sporadic MND and 5 age-matched controls. This was compared with the expression of ubiquitin, p62 and TDP-43 and its phosphorylated form. The principal finding was the increased expression of the endosomal marker Rab5 and lysosomal cathepsin D, and of PAS-positive structures in motor neurons of MND cases. Furthermore, the area-portion of Rab5 immunoreactivity correlated well with the intracellular accumulation of ubiquitin, p62 and (phosphorylated) TDP-43. However, double immunolabelling and immunogold electron microscopy excluded colocalization of phosphorylated TDP-43 with the ELS. These data contrast with observations on neuronal cytopathology in Alzheimer's or prion diseases where the disease-specific proteins are processed within endosomes, and suggest a distinct role of the ELS in MND.

Original languageEnglish
Pages (from-to)133-139
Number of pages7
JournalExperimental Neurology
Issue number1
Publication statusPublished - Sep 1 2010


  • Cathepsin
  • Endosome
  • Lysosome
  • Motor neuron disease
  • Rab5
  • TDP-43
  • Ubiquitin

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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