Skip to main content
Fig. 1 | Acta Neuropathologica Communications

Fig. 1

From: Deposition of mutant ubiquitin in parkinsonism–dementia complex of Guam

Fig. 1

Mutant ubiquitin (UBB+1) is deposited in Guam parkinsonism–dementia complex (G-PDC) brains. a UBB+1 is generated through “molecular misreading”, a type of transcriptional mutagenesis. The resulting unfaithful RNA messengers can generate abnormal proteins with cytotoxic properties. b UBB+1 contains an extended C-terminal domain, which can be recognized by anti-UBB+1 antibodies. Deubiquitating enzymes (DUBs) can hydrolyze this extended C-terminus. However, inhibition of these DUBs, e.g., by oxidative stress conditions, prevents this cleavage, preserving the epitope [2]. c-e Immunostaining for UBB+1 (Ubi2A, 1:400, Dr. F.W. van Leeuwen [3]) reveals many cytoplasmic structures in neurons and glial cells (i.e., astrocytes in the alveus and stratum oriens) of the hippocampus. f-h Additionally, cytoplasmic TAR DNA-binding protein 43 (TDP-43) aggregates can be observed in the same cell types (mouse anti-TDP-43, 1:1000, Abnova). i-k Aggregates containing ubiquitin C-terminal hydrolase L1 (UCH-L1) (rabbit anti-UCH-L1, 1:500, Biomol), a DUB, and l-n Rpt3/S6b (rabbit anti-Rpt3, 1:400, Biomol), a proteasomal subunit [13], are also found in G-PDC. Several immunoreactive structures show a granular staining pattern (arrowheads). All immunostainings were carried out on 6 μm thick formalin-fixed, paraffin-embedded sections. Panels c-n all show representative images of G-PDC hippocampi (adjacent sections from subject #2, Table 1). Scale bars 200 μm (c, f, i, l), 100 μm (d, g, j, m), and 50 μm (e, h, k, n)

Back to article page