Antibody to an abnormal protein in amyotrophic lateral sclerosis identifies Lewy body-like inclusions in ALS and Lewy bodies in Parkinson's disease

The evidence for altered RNA metabolism in amyotrophic lateral sclerosis (ALS)

“…TDP-43 can tether DNA to the nuclear matrix and subnuclear membrane to maintain it in a transcriptionally inactive state [128], and can act as a splicing regulator [129,130]. While the classic TDP-43 DNA or RNA interactions have been described as requiring (TG) [6][7][8][9][10][11][12] or (UG) [6][7][8][9][10][11][12] repeat motifs, interestingly, TDP-43 regulation of HIV-1 gene expression occurs by the recognition of a motif consisting of a polypyrimide rich region [127]. This exception to the "rule" of TDP-43 binding through UG/ TG repeats is important when we consider the interaction of TDP-43 with NFL mRNA where no UG repeats are evident [92,124].…”

“…Pathological intracellular protein aggregates are amongst the neuropathological hallmarks of ALS and can consist of one or more of the intermediate filament proteins (neurofilament proteins (NF) [9], α-internexin [10] or peripherin [11]), 14-3-3 proteins [12,13], copper/zinc superoxide dismutase (SOD1) [14][15][16], TAR DNA binding protein of 43 kDa (TDP-43) [17,18] and the recently described chromosome 16 linked fused in sarcoma/translated in liposarcoma gene product (FUS/TLS) ( Fig. 1) [19,20].…”

Therapeutic induction of autophagy to modulate neurodegenerative disease progression

“…Mitochondrial damage and abnormal protein inclusions such as Lewy bodies 20 , Skein inclusions 21 and Bunina inclusions 22 are the characteristic pathological features in ALS. ALS can be caused by mutations in a number of different genes.…”

Involvement of tubulin in MPP+ neurotoxicity on NGF‐differentiated PC12 cells.

“…Most of these inclusions are made of abnormal filaments and share epitopes with cytoskeletal proteins. One of these inclusions, the Lewy bodies of Parkinson's Disease (PO), has been shown to react with antibodies against tubulin and various microtubule-associated proteins (Galloway et ai, 1988), phosphorylated and non-phosphorylated neurofilaments (Forno et al, 1986) and abnormal protein probably related to actin (Mather et al, 1993). 1065-6995/95/080687 +07/$12.0010 In a previous study (Cappelletti et aI, 1991), we showed the cytoskeleton involvement in the starting events of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) cytotoxicity on cultured mouse fibroblasts.…”