Advertisement
Research Article| Volume 249, ISSUE 1, P13-18, November 01, 2006

Download started.

Ok

Immunoreactivities of p62, an ubiqutin-binding protein, in the spinal anterior horn cells of patients with amyotrophic lateral sclerosis

      Abstract

      An ubiquitin-binding protein, p62, is one of the components of the ubiquitin-containing inclusions in several human neurodegenerative diseases. Amyotrophic lateral sclerosis (ALS) is characterized by the presence of skein-like inclusions, Lewy body-like inclusions, and basophilic inclusions in the remaining anterior horn cells, in which these inclusions contain ubiquitin, while the other characteristic inclusions of Bunina type are ubiquitin-negative. We examined the spinal cord from 28 ALS cases including two ALS with dementia and two ALS with basophilic inclusions, using antibody to p62. The results demonstrated that p62 localized in skein-like inclusions, Lewy body-like inclusions and basophilic inclusions. The number of p62-positive inclusions observed in the remaining anterior horn cells of each section was variable among the ALS cases. In contrast, Bunina bodies, that do not contain ubiquitin, were negative for p62. As far as we examined, the 11 non-ALS cases did not show any p62 immunoreactivities in the anterior horn cells. Our results suggested that p62 plays important roles in forming the inclusions and may be associated with the protection of the neurons from degenerative processes involving ubiquitin.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of the Neurological Sciences
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Okamoto K.
        • Hirai S.
        • Amari M.
        • Watanabe M.
        • Sakurai A.
        Bunina bodies in amyotrophic lateral sclerosis immunostained with rabbit anti-cystatin C serum.
        Neurosci Lett. 1993; 162: 125-128
        • Leigh P.N.
        • Anderton B.H.
        • Dodson A.
        • Gallo J.M.
        • Swash M.
        • Power D.M.
        Ubiquitin deposits in anterior horn cells in motor neurone disease.
        Neurosci Lett. 1988; 93: 197-203
        • Mizusawa H.
        • Hirano A.
        • Yen S.H.C.
        Anterior horn cell inclusions in familial amyotrophic lateral sclerosis contain ubiqutin and phosphorylated neurofilament epitopes.
        Neuropathology. 1991; 11: 11-20
        • Kato T.
        • Katagiri T.
        • Hirano A.
        • Kawanami T.
        • Sasaki H.
        Lewy body-like hyaline inclusions in sporadic motor neuron disease are ubiquitinated.
        Acta Neuropathol (Berl). 1989; 77: 391-396
        • Fujita Y.
        • Okamoto K.
        • Sakurai A.
        • Kusaka H.
        • Aizawa H.
        • Mihara B.
        • et al.
        The Golgi apparatus is fragmented in spinal cord motor neurons of amyotrophic lateral sclerosis with basophilic inclusions.
        Acta Neuropathol (Berl). 2002; 103: 243-247
        • Park I.
        • Chung J.
        • Walsh C.T.
        • Yun Y.
        • Strominger J.L.
        • Shin J.
        Phosphotyrosine-independent binding of a 62-kDa protein to the src homology 2 (SH2) domain of p56lck and its regulation by phosphorylation of Ser-59 in the lck unique N-terminal region.
        Proc Natl Acad Sci U S A. 1995; 92: 12338-12342
        • Janig E.
        • Stumptner C.
        • Fuchsbichler A.
        • Denk H.
        • Zatloukal K.
        Interaction of stress proteins with misfolded keratins.
        Eur J Cell Biol. 2005; 84: 329-339
        • Zatloukal K.
        • Stumptner C.
        • Fuchsbichler A.
        • Heid H.
        • Schnoelzer M.
        • Kenner L.
        • et al.
        p62 is a common component of cytoplasmic inclusions in protein aggregation diseases.
        Am J Pathol. 2002; 160: 255-263
        • Kuusisto E.
        • Suuronen T.
        • Salminen A.
        Ubiquitin-binding protein p62 expression is induced during apoptosis and proteasomal inhibition in neuronal cells.
        Biochem Biophys Res Commun. 2001; 280: 223-228
        • Kuusisto E.
        • Salminen A.
        • Alafuzoff I.
        Early accumulation of p62 in neurofibrillary tangles in Alzheimer's disease: possible role in tangle formation.
        Neuropathol Appl Neurobiol. 2002; 28: 228-237
        • Kuusisto E.
        • Salminen A.
        • Alafuzoff I.
        Ubiquitin-binding protein p62 is present in neuronal and glial inclusions in human tauopathies and synucleinopathies.
        NeuroReport. 2001; 12: 2085-2090
        • Nakano T.
        • Nakaso K.
        • Nakashima K.
        • Ohama E.
        Expression of ubiquitin-binding protein p62 in ubiquitin-immunoreactive intraneuronal inclusions in amyotrophic lateral sclerosis with dementia: analysis of five autopsy cases with broad clinicopathological spectrum.
        Acta Neuropathol (Berl). 2004; 107: 359-364
        • Okamoto K.
        • Hirai S.
        • Yamazaki T.
        • Sun X.Y.
        • Nakazato Y.
        New ubiquitin-positive intraneuronal inclusions in the extra-motor cortices in patients with amyotrophic lateral sclerosis.
        Neurosci Lett. 1991; 129: 233-236
        • Vadlamudi R.K.
        • Joung I.
        • Strominger J.L.
        • Shin J.
        p62, a phosphotyrosine-independent ligand of the SH2 domain of p56lck, belongs to a new class of ubiquitin-binding proteins.
        J Biol Chem. 1996; 271: 20235-20237
        • Ciechanover A.
        The ubiquitin–proteasome proteolytic pathway.
        Cell. 1994; 79: 13-21
        • Stumptner C.
        • Heid H.
        • Fuchsbichler A.
        • Hauser H.
        • Mischinger H.J.
        • Zatloukal K.
        • et al.
        Analysis of intracytoplasmic hyaline bodies in a hepatocellular carcinoma. Demonstration of p62 as major constituent.
        Am J Pathol. 1999; 154: 1701-1710