Literature: A-K ; L-Z ; subject area
Compiled by: Julian Thorpe
Our Group's Research on Pin1 in AD and FTD Brain
Funded by
***** See the University Press Release about our Grant *****
Dr. Nigel Cairns, courtesy of the Brain Bank at the Institute of Psychiatry , King's College London and the Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania, PA, USA
Publications ; Conferences/Seminars ; Conference Posters ; 'BRAIN' Group Meetings ; Previous Relevant Publications
Summary of Our Published Research ; Our TEM-based Research
 | We have developed a novel transmission electron
microscope (TEM) methodology whereby the PPIase protein Pin1 is
used as a probe for its target proteins within tissues (Thorpe et al., 1999
). See more detail on the methodology of using chaperone proteins
as 'TEM Probes
' of their target proteins. |
| Previously, we have utilised this latter methodology in work including a preliminary examination (restricted to one brain sample) of the levels and distribution of both endogenous Pin1 and exogenous Pin1 binding in (normal and) AD human brain ( Thorpe et al., 2001 ; see figures below). This work showed enhanced levels of Pin1 binding to its (unbound, phosphorylated) target proteins inAD (compared with normal) brain. In AD-affected neurones, immunolabelling for endogenous Pin1 showed a redirection to the cytoplasm (compared with normal neurons [white bars in figures below]), while the highest levels of (exogenous) Pin1 binding were to the tau-immunoreactive tangles , reflecting the large amounts of phosphorylated tau and indicative of a shortfall of available Pin1 in these cells (grey bars in figures below). |
Pin1 immunolabelling densities over neuronal nuclei (Nu), cytoplasm (Cyt) and tau-immunoreactive tangles (Tau) in normal and AD brain sections incubated in buffer alone (revealing endogenous Pin1 levels; 'End' - white bars) or in 20ug/ml Pin1 protein (revealing endogenous Pin1 levels plus exogenous Pin1 binding; End/Exo - black bars). Grey bars ('Exo') represent levels of exogenous Pin1 binding (End/Exo minus End). All sections subsequently immunolabelled with (goat) anti-Pin1 antiserum followed by rabbit anti-goat gold probe. Pooled results from 3 separate immunolabellings. Data = gold particles/um2; n = 30 +/- sem. (from Thorpe et al., 2001 )
|
Recently, we have
extended this work to examine a range of frontotemporal dementias
(FTDs; Thorpe
et al., 2004). |
|
We found that similar Pin1 redistribution and shortfalls occur in neurons affected by FTDs characterized by abnormal protein aggregates of tau and other cytoskeletal proteins. |
Endogenous Pin1:
Exogenous Rec-Pin1 Binding:
|
We
suggested that, as
nuclear Pin1 depletion causes apoptosis, shortfalls in regard to both
nuclear and p-tau targets may contribute to neuronal dysfunction. |
|
Therefore,
this might be a unifying, contributory factor towards neuronal death in
these dementias. |
| See TEM images of tangles immunogold labelled for tau protein |
| N.B. See the author's Lab Website for full details on immunogold labelling TEM |
Articles:
Page
T, Gitcho MA, Mosaheb S, Carter D,Chakraverty S, Perry RH, Bigio EH, Gearing M,
Ferrer I, Goate AM, Cairns NJ, Thorpe JR (2011) FUS
immunogold labelling TEM analysis of the neuronal cytoplasmic inclusions of
neuronal intermediate filament inclusion disease: a frontotemporal lobar
degeneration with FUS proteinopathy. Journal of Molecular Neuroscience 45:
409-421 DOI: 10.1007/s12031-011-9549-8
Thorpe JR, Tang HHL, Atherton JM, Cairns NJ (2008) Fine structural analysis of the neuronal inclusions of frontotemporal lobar degeneration with TDP-43 proteinopathy. Journal of Neural Transmission 115: 1661-1671
Hashemzadeh-Bonehi L, Phillips RG, Cairns NJ, Mosaheb S, Thorpe JR (2006) Pin1 protein associates with neuronal lipofuscin: potential consequences in age-related neurodegeneration. Experimental Neurology 199: 328-338
Momeni P, Cairns NJ, Perry RH, Bigio E, Gearing M, Singleton AB, Hardy J. (2006). Mutation analysis of patients with neuronal intermediate filament inclusion disease. Neurobiology of Aging 27: 778.e1-778.e6
Mosaheb S,
Thorpe JR, Hashemzadeh-Bonehi
L,Bigio EH,Gearing M, Cairns NJ
(2005)
Neuronal
intranuclear inclusions are ultrastructurally and immunologically distinct
from cytoplasmic inclusions of neuronal intermediate filament inclusion
disease (NIFID). Acta Neuropathologica
Cairns NJ, Lee V M-Y, Trojanowski JQ (2004) The cytoskeleton in neurodegenerative diseases (review article). Journal of Pathology 204: 438-449
Thorpe
JR, Mosaheb S, Hashemzadeh-Bonehi L, Cairns NJ, Kay KE, Morley SJ, Rulten S (2004)
Shortfalls in the Peptidyl-Prolyl Cis-Trans
Isomerase Protein Pin1 in Neurons are Associated With Frontotemporal
Dementias. Neurobiology of Disease
Cairns
NJ, Grossman M, Arnold SE, Burn DJ, Jaros E, Perry RH,
Duyckaerts C, Stankoff B, Pillon B, Skullerud K, Cruz-Sanchez FF,
Bigio EH, Mackenzie IRA, Gearing M, Juncos JL, Glass JD, Yokoo H, Nakazato
Y, Mosaheb S, Thorpe JR, Uryu K, Lee V.M.-Y, Trojanowski, JQ (2004)
Clinical and
neuropathologic variation in neuronal intermediate filament inclusion
disease (NIFID). Neurology
63:
1376-1384
Cairns
NJ, Uryu K, Bigio E, Mackenzie IRA, Gearing M, Duyckaerts C, Yokoo H,
Nakazato Y, Jaros E, Perry RH, Arnold SE, Lee V M-Y, Trojanowski JQ (2004) a-Internexin is a major component
of the pathological inclusions of neuronal intermediate filament inclusion
disease (NIFID) and a minor component of other neurodegenerative diseases. Acta
Neuropathologica
Cairns NJ, Zhukareva V, Uryu K, Zhang B, Bigio E, Mackenzie IRA,
Gearing M, Duyckaerts C, Yokoo H, Nakazato Y, Jaros E, Perry RH, Lee VM-Y,
Trojanowski JQ (2004) a-Internexin is Present in the Pathological Inclusions
of Neuronal Intermediate Filament Inclusion Disease. Am J Pathol 164:
2153-2161
Thorpe JR (2006) Are ageing and neurodegenerative brain neurons Pining for a protein? The involvement of Pin1 protein in ageing-related brain neurodegeneration. School of Pharmacy and Biomolecular Sciences. University of Brighton, November 29th., 2006
Thorpe JR (2006) Are ageing and neurodegenerative brain neurons Pining for a protein? The evidence for the case that redressing neuronal Pin1 deficits could be a potential therapeutic strategy. Biochemistry, Genetics and Development Group Seminars. University of Sussex, June 6th., 2006
Thorpe JR (2005) Are Neuronal Deficits of the Cell Cycle and Tau-Regulating Protein Pin1 a Linking Contributory Factor in Brain Ageing and Neurodegeneration? Sussex Centre for Neuroscience Seminars. University of Sussex, June 20th., 2005
Mosaheb S, Hashemzadeh-Bonehi L,
Rulten SL, Kay JE, Thorpe JR and Cairns
NJ (2005) Fine
structure of intranuclear inclusions in neuronal intermediate filament inclusion
disease. The 81st Annual Meeting of
the American Association of Neuropathologists, Inc. Hyatt Regency Crystal
City Arlington, VA June 9-12, 2005. Journal
of Neuropathology and Experimental Neurology 64: 70
Mosaheb S (2005) Characterisation of intranuclear inclusions in neuronal intermediate filament disease. Electron Microscope Users Meeting - South. University of Sussex, June 8th., 2005. Royal Microscopical Society Proceedings 40: 199
Hashemzadeh-Bonehi L, Mosaheb S, Cairns
NJ, Rulten SL, Kay JE, Phillips RG and Thorpe JR (2005) Neuronal
Shortfalls and Localisation to Lipofuscin of the Cell Cycle and Tau-Regulating
Protein Pin1: A Linking Susceptibility Factor for Ageing and
Neurodegeneration? Second Meeting on the Molecular Mechanisms of
Neurodegeneration, Aula Magna, Universita'
degli Studi di Milano, Via Festa
del Perdono 7, 20122 - Milano (Italy) May
7-10, 2005
Thorpe JR (2004) Intraneuronal damage responsible for
Alzheimer's disease and other dementias.
'New
Approaches in Dementia', University of Brighton. October 6th. 2004
Thorpe JR, Mosaheb S, Hashemzadeh-Bonehi
L, Cairns NJ, Kay KE, Morley SJ, Rulten S (2004) Shortfalls in the Peptidyl-Prolyl Cis-Trans
Isomerase Protein Pin1 in Neurons are Associated With Frontotemporal
Dementias.
Brighton and Sussex Medical School
Research Day June 30th. 2004
Cairns NJ, Jaros E, Perry R, Bigio E,
Thorpe JR, Mosaheb S, Zhang B, Lee V M-Y,Trojanowski JQ (2003)
Phophorylated neurofilaments form abnormal aggregates in Dementia with
Neurofilament Inclusions. Program No. 875.4 Society for Neuroscience 33rd.
Annual Meeting, New Orleans, November 8-12, 2003
Hashemzadeh-Bonehi
L, Phillips RG and Thorpe JR (2005)
A
Novel Localisation of the Peptidyl-Prolyl Cis-Trans Isomerase
Protein Pin1
to Neuronal Lipofuscin Granules in Ageing and Neurodegeneration
Revealed by Correlative Light and Transmission Electron Microscopy. Second Meeting on the Molecular Mechanisms of
Neurodegeneration, Aula Magna, Universita'
degli Studi di Milano, Via Festa
del Perdono 7, 20122 - Milano (Italy) May
7-10, 2005
Hashemzadeh-Bonehi L, Mosaheb S, Cairns NJ, Rulten S, Kay KE, Phillips RG, Thorpe JR (2005) Are Shortfalls in the Cell Cycle and Tau-Regulating Protein Pin1 a Susceptibility Factor for Neurodegeneration and Ageing? Molecular Mechanisms of Neurodegeneration: a Joint Biochemical Society/Neuroscience Ireland Focused Meeting. University College, Dublin, Republic of Ireland. March 14th-16th 2005
Mosaheb S, Hashemzadeh-Bonehi L, Cairns NJ, Kay JE, Morley SJ, Rulten SL and Thorpe JR (2004) Shortfalls in the Peptidyl-Prolyl Cis-Trans Isomerase Protein Pin1 in Neurons are Associated With Frontotemporal Dementias. FTD Satellite Conference, University of Pennsylvania, July 15-16th. 2004
Cairns NJ,
Grossman M, Arnold SE, Burn DJ, Jaros E, Perry RH, Duyckaerts C, Stankoff B,
Skullerud K, Cruz-Sanchez FF, Bigio EH, Mackenzie IRA, Gearing M, Yokoo H,
Nakazato Y, Mosaheb S,Thorpe JR, Uryu K, Lee VM-Y, Trojanowski JQ
(2004) Clinical and Neuropathologic Variation in Neuronal
Intermediate Filament Inclusion Disease (NIFID) 9th International Conference on
Alzheimer's Disease, Frontotemporal Dementia Satellite Meeting, University of
Pennsylvania July 15-16th, 2004
Mosaheb S, Hashemzadeh-Bonehi L, Cairns NJ, Kay JE, Morley SJ, Rulten SL and Thorpe JR (2004) Shortfalls in the Peptidyl-Prolyl Cis-Trans Isomerase Protein Pin1 in Neurons are Associated With Frontotemporal Dementias. Brighton and Sussex Medical School Research Day June 30th. 2004
'BRAIN' (Bridging Research Areas in Neurodegeneration) Group Meetings: This group aims to bring together local researchers and clinicians with interests in aspects of human neurodegenerative diseases. Coordinated by Sabrina Mosaheb.
(1/10/04) Brighton and Sussex Medical School. who described his work on the genetic and molecular basis for familial motor neurone disease.
Our Previous Publications (leading up to our present project)):
Thorpe
JR, Morley SJ, Rulten SL (2001)
Utilising the Peptidyl-Prolyl Cis-Trans Isomerase Pin1 as a Probe of its
Phosphorylated Target Proteins: Examples of Binding to Nuclear Proteins in a
Human Kidney Cell Line and to Tau in Alzheimer’s Diseased Brain.
J. Histochem. Cytochem. 49: 97-108
Thorpe
JR, Rulten SL, Kay JE (1999)
The binding of a putative and a known chaperone protein revealed by immunogold
labelling transmission electron microscopy: A suggested use of chaperones as
probes for the distribution of their target proteins.
J. Histochem. Cytochem. 47, 1633-1640
Rulten
SL, Thorpe JR, Kay JE (1999)
Identification of Eukaryotic Parvulin Homologues: A new subfamily of
peptidyl-prolyl cis-trans isomerases.
Biochem Biophys Res Comm 259: 557-562