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Neurodegenerative diseases
 
January 22 - 26
Paula Agostinho, Claudia Pereira, Cristina Rego e Luis Almeida
Coordinators:
Ana Cristina Rego
Cláudia Pereira
Luís Pereira de Almeida
Paula Agostinho
Center for Neuroscience and Cell Biology, University of Coimbra

See photo group [open]


Invited Lecturers:
Olga Corti, INSERM U679 (former U289)- Thérapeutique et Neurologie Expérimentale Hôpital de la Pitié-Salpêtriére, Paris, France
Ruth Luthi-Carter, Laboratoire de Neurogénomique Functionelle, École Polytechnique Fédérale de Lausanne, Lausanne, Suisse
Salvatore Oddo, Laboratory of Molecular Neuropathogenesis, Department
of Neurobiology and Behavior, University of California, Irvine, USA


Aim of the course:
This course will focus on the latest research in the field of neurodegenerative diseases, focusing on Alzheimer disease (AD), Parkinson disease (PD) and Huntington disease (HD).
AD is the most common form of dementia in the elderly. The risk of AD dramatically increases with aging and it is predicted that the incidence of AD will increase threefold within the next 50 years if no therapy intervenes. In developed societies where life expectancy has been considerably extended, this devastating disease actually
represents a major public health concern.
PD is the second most-common neurodegenerative disorder affecting about 2% of the
population over 65 years of age. Despite major advances over the last decade, the etiology of PD remains unclear. Occurring most commonly as the sporadic idiopathic form, PD has been hypothesized to be attributed to genetic predisposition to either endogenous toxins or environmental factors, such as pesticides, herbicides and industrial chemicals.
HD is a polyglutamine expansion disease caused by expansion of CAG repeat mutations in the coding region of huntingtin. The disease exhibits gradual progression of symptoms that finally result in the death of the patients. Despite the identification of the genetic defects, the mechanism by which the mutant protein initiates the pathogenic process remains to be elucidated. This is also common to AD and PD.
Thus, this course is intended to promote the understanding of molecular mechanisms operating in these diseases. Although there is currently no cure for these devastating neurodegenerative disorders, new treatments are on the horizon as a result of accelerating insights into the biology of the diseases. Moreover, these neurodegenerative diseases are a current focus of research by several groups at the CNC.


Student’s Assignments:
This course is mandatory for Ph.D. students following the CNC Programme in Experimental Biology
and Biomedicine (PDBEB), but is open to other students.
PDBEB students (and other Ph.D. students who wish to participate for credit), in groups of 3-4 students,
will be asked to consider an assigned paper as representing a pivotal work and prepare a brief project stating
what experiments would be important to do next. While briefly mentioning the paper findings, the students
should concentrate on which directions the research would take.
The first step will be submitting a letter of intent (LOI) which must include, in one A4 page, the name of the
investigators, the title of the investigation, area of focus of the submission and a brief rationale for the proposal.
The deadline for LOI submission is Wednesday (January 24) morning and the fictive projects will be presented
and discussed during Friday (January 26) morning.
The guidelines for the Power Point presentation of the projects are the following:
Title
State of the Art
Objectives
Tasks (maximum 3, including expected results and descriptions)
Research Team
Masters students enrolled in the Masters in Cell Biology Program at the Department of Zoology will be asked to
present and discuss assigned papers (i.e., PowerPoint presentations) on Thursday (January 25) afternoon.


Reading assignments for Ph.D. students
Alzheimer disease
Lesne S, Koh MT, Kotilinek L, Kayed R, Glabe CG, Yang A, Gallagher M, Ashe KH. (2006) A specific amyloid-beta
protein assembly in the brain impairs memory
Nature 440: 352-357.
Students presenting: Joana Neves / Vera Ribeiro / Rui Costa / Pedro Garção
.
Klyubin I, Walsh DM, Lemere CA, Cullen WK, Shankar GM, Betts V, Spooner ET, Jiang L, Anwyl R, Selkoe DJ, Rowan MJ (2005) Amyloid beta proteinimmunotherapy neutralizes Abeta oligomers that disrupt synaptic plasticity in vivoStudents presenting: Sofia Grade / Daniel Nunes / Elisabete Ferreiro. Nat. Med. 11:556-561. 



Reading assignments for Masters students

Alzheimer disease
Oddo S, Vasilevko V, Caccamo A, Kitazawa M, Cribbs DH, Laferla FM. (2006) Reduction of soluble Abeta and tau,
but not soluble Abeta alone, ameliorates cognitive decline in transgenic mice with plaques and tangles
J. Biol. Chem. 281: 39413-3923.
Students presenting: Ana Filipa Domingues / João Filipe Martins

Parkinson disease
Periquet M, Corti O, Jacquier S, Brice A (2005)
Proteomic analysis of parkin knockout mice: alterations in energy
metabolism, protein handling and synaptic function
J. Neurochem. 95: 1259-1276.
Students presenting: Luís Bimbo / Sueli Marques

Polyglutamine diseases
Yamamoto A, Cremona ML, Rothman JE (2006)
Autophagy-mediated clearance of huntingtin aggregates triggered by the insulin-signaling pathwayJ. Cell Biol. 172: 719–731.
Students presenting: Vanessa Matos / Susana Louros / Raquel Vinhais
. . .
 
Course Schedule:
Monday (Jan 22)
10:00-10:15 Presentation of the contents, teachers and goals of the course

10:15-10:45 Introduction to Alzheimer disease. What goes on at CNC?
...................Paula Agostinho / Cláudia Pereira

10:45-11:45 Introduction to polyglutamine expansion diseases. What goes on at CNC?
...................Ana Cristina Rego / Luís Pereira de Almeida
14:00-15:00 Parkinson´s disease: clinical, neuropathological and genetic aspects
...................Olga Corti
15:00-16:00 Transcriptional dysregulation in polyglutamine diseases
....................Ruth Luthi-Carter
Tuesday (Jan 23)
09:00-10:00 Alzheimer disease: from genes to animal models
...................Salvatore Oddo

10:00-10:30 Coffee Break

10:30-11:30 Modeling plaques and tangles in the same animal
...................Salvatore Oddo

14:00-15:00 Gene expression profiling in polyglutamine diseases
...................Ruth Luthi-Carter

15:00-16:00 Autophagy-mediated neuroprotection against polyglutamine disease
...................Ruth Luthi-Carter

19:30 ......... Dinner
Wednesday (Jan 24)
Deadline for LOI submission
09:00-10:00 Modulation of polyglutamine disease by micro RNA
...................Ruth Luthi-Carter

10:00-10:30 Coffee Break

10:30-11:30 Dysfunction of protein degradation pathways in Parkinson´s disease
...................Olga Corti

14:00-15:00 The role of mitochondria in the pathogenesis of Parkinson´s disease
...................Olga Corti

15:00-16:00 Cholinergic system in Alzheimer disease
...................Salvatore Oddo
Thursday (Jan 25)
10:30-11:30 Abeta immunization in Alzheimer disease
...................Salvatore Oddo

14:30-15:30 Journal Club (Master students)
Friday (Jan 26)
09:00-11:30 Projects presentation by Ph.D. Students
16:00-17:00 Seminar: From Parkin gene mutations to Parkinson’s disease: Pieces of the puzzle
...................Olga Corti
 
Affiliation and contacts:
Invited lecturers
Olga Corti (Ph.D., Researcher), INSERM U679 (former U289)- Thérapeutique et Neurologie Expérimentale
Hôpital de la Pitié-Salpêtriére, Bâtiment Pharmacie, 4éme étage, 47 boulevard de l’Hôpital, 75013 Paris, France 
Tel (01) 42162217/23; Fax (01) 44243658; E-mail corti@ccr.jussieu.fr
Ruth Luthi-Carter (Ph.D., Assistant Professor), Laboratoire de Neurogénomique Functionelle, École
Polytechnique Fédérale de Lausanne, Bâtiment AI 2138, Station 15, CH-1015 Lausanne, Suisse
Tel (41) 21 6939533; E-mail ruth.luthi-carter@epfl.ch
Salvatore Oddo (Ph.D., Postdoctoral Researcher), Laboratory of Molecular Neuropathogenesis, Department
of Neurobiology and Behavior, 1216 Gillespie Neuroscience, Irvine, CA 92697, USA
Tel (949) 824 3471; Fax (949) 824 7356; E-mail soddo@uci.edu


Coordinators
Ana Cristina Rego (Ph.D., Assistant Professor), Center for Neuroscience and Cell Biology & Faculty of Medicine,
University of Coimbra, 3004-504 Coimbra, Portugal
Tel (351) 239 820190; Fax (351) 239 822776; E-mail acrego@cnc.cj.uc.pt
Cláudia Pereira (Ph.D., Research Associate), Center for Neuroscience and Cell Biology & Faculty of Medicine,
University of Coimbra, 3004-504 Coimbra, Portugal
Tel (351) 239 820190; Fax (351) 239 822776; E-mail cpereira@cnc.cj.uc.pt
Luís Pereira de Almeida (Ph.D., Assistant Professor), Center for Neuroscience and Cell Biology, Faculty of
Pharmacy, University of Coimbra, 3000-295 Coimbra, Portugal
Tel (351) 239 859927; Fax (351) 239 827126; E-mail luispa@ci.uc.pt
Paula Agostinho (Ph.D. Research Associate), Center for Neuroscience and Cell Biology, Faculty of Medicine,
University of Coimbra, 3004-504 Coimbra, Portugal
Tel (351) 239 820190; Fax (351) 239 822776; E-mail pagost@cnc.cj.uc.pt

Publications of invited speakers and coordinators
:
Invited speakers
Olga Corti
Ruth Luthi-Carter
Hodges A, Strand AD, Aragaki AK, Kuhn A, Sengstag T, Hughes G, Elliston LA, Hartog C, Goldstein DR,
Thu D, Hollingsworth ZR, Collin F, Synek B, Holmans PA, Young AB, Wexler NS, Delorenzi M, Kooperberg C,
Augood SJ, Faull RL, Olson JM, Jones L, Luthi-Carter R (2006) Regional and cellular gene expression changes
in human Huntington´s disease brain
. Hum. Mol. Genet. 15: 965-977.
Luthi-Carter R, Strand AD, Hanson SA, Kooperberg C, Schilling G, La Spada AR, Merry DE, Young AB,
Ross CA, Borchelt DR, Olson JM. (2002)Polyglutamine and transcription: gene expression changes shared
by DRPLA and Huntington´s disease mouse models reveal context-independent effects
. Hum. Mol. Genet.
11: 1927-1937.
Salvatore Oddo
Oddo S, Caccamo A, Green K, Liang K, Tran L, Chen Y, Leslie FM, LaFerla FM (2005)  Chronic nicotine
administration exacerbates tau pathology in a transgenic model of Alzheimer´s disease
Proc. Natl. Acad. Sci.
USA
102: 3046-3051.
Oddo S, Caccamo A, Shepherd JD, Murphy MP, Golde TE, Kayed R, Metherate R, Mattson MP, Akbari Y,
LaFerla FM (2003)  Triple transgenic model of Alzheimer´s disease with plaques and tangles: intracellular Aß
and synaptic dysfunction
Neuron 39: 409-421.


Coordinators
Ana Cristina Rego
Oliveira JM, Chen S, Almeida S, Riley R, Goncalves J, Oliveira CR, Hayden MR, Nicholls DG, Ellerby LM,
Rego AC
(2006) Mitochondrial-dependent Ca2+ handling in Huntington´s disease striatal cells: effect of
histone deacetylase inhibitors
. J. Neurosci. 26: 11174-11186.
Almeida S, Domingues A, Rodrigues L, Oliveira CR, Rego AC (2004) FK506 prevents mitochondrial-dependent
apoptotic cell death induced by 3-nitropropionic acid in rat primary cortical cultures.
Neurobiol. Dis. 17: 435-444.
Cláudia Pereira
Luís Pereira de Almeida
Rego AC, de Almeida LP (2005) Molecular targets and therapeutic strategies in Huntington´s disease. Curr.
Drug Targets CNS Neurol. Disord.
4: 361-381. Review
Paula Agostinho 
 
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