Members: Ashkan Azimi, Sabrina Cheung, Tiera Dookhie, Farhiya Elmi, Suban Farah, Hajrah Gul, Muhammed Aashiq Rahman, Andrey Son

A neurodegenerative disease (NDD) is a condition that affects central and/or peripheral nervous system function. As the name implies, it is characterized by degeneration of neural function after development. The degeneration of a specific neuronal subset is associated with each individual NDD.1 The clinical presentations of NDDs typically appear after substantial neuronal loss. Neuronal cell death accompanying a given disease is associated with extracellular plaques, intracellular inclusions of factors/proteins, or a slow degradation of molecular factors2. Some proteins can be the direct cause of cell death, or the indirect cause via compensatory mechanisms such as mitochondrial dis-regulation. Neurodegenerative diseases can be categorized into two groups; ones that affect cognitive function (memory, language etc.) or ones that affect motor functions. These diseases are typically known to occur in the elderly because of the late age of onset; however this is not always the case (see Multiple Sclerosis)3. Individuals with a NDD can only get a probable diagnosis due to overlapping clinical presentations between diseases, and a definitive diagnosis can only be made post mortem. Sadly, there are no cures for NDDs; only treatments for the symptoms that arise from them. Huntington’s disease (HD) is an important disease to look at when understanding the impact of NDDs. It arises from a mutation within the HTT protein that causes the disruption and degeneration of neurons leading to physical deterioration and mental loss. Treatments for HD, like other NDDs, are only symptomatic with no preventative cure. In addition, there is also Parkinson’s disease; a progressive motor disorder that generally affects older individuals due to destruction of dopaminergic neurons in the substantia nigra. Another example of a NDD, Friedreich's ataxia, is the most common inherited ataxia. It is characterized by progressive nervous system damage leading to weakened muscle coordination. Prions can also cause neurodegenerative diseases such as Creutzfeldt-Jakob disease and Kuru. However, the cellular form of prions are not disease causing and there is evidence to believe that they may serve some neuroprotective function as well as control emotions. Lastly, recent evidence shows similar prion-like characteristics of some proteins associated with NDDs. With the aging of the baby boomer generation in Canada, increasing incidence rates of NDDs will have a significant impact on our economy and health care system. Numerous studies are currently conducted to determine causes and more effective treatment options.

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1. Huntington’s Disease

1.1 Genetic characteristics (F. Elmi)
  • 1.1.1 The role of the IT15 gene and amplification of CAG repeats
  • 1.1.2 Molecular effects caused by DNA alteration in the IT15 gene
  • 1.1.3 Inheritance
1.2 Symptoms
  • 1.2.1 Age of onset
  • 1.2.2 Common behavioural and physical manifestations
1.3 Prognosis
  • 1.3.1 Association between CAG trinucleotide repeats and gradual progression of HD
  • 1.3.2 Fatality as a result of infection and other agencies
1.4 Diagnosis (H. Gul)
  • 1.4.1 Clinical Assessment
  • 1.4.2 Neuroimaging
  • 1.4.3 Genetic testing
  • 1.4.4 Prenatal testing
1.5 Treatment
  • 1.5.1 Therapy treatment
  • 1.5.2 Drug treatment
  • 1.5.3 Side Effects

2. Parkinson’s Disease

2.1 Genetics (A. Azimi)
  • 2.1.1 List of Genes contributing to different phenotypes of Parkinson’s
  • 2.1.2 Parkin (PARK2) Overview
  • 2.1.3 Proposed Biological Function
  • 2.1.4 PARK2 Animal Knockout Models
  • 2.1.4a PARK2 Drosophila knockout model
  • 2.1.4b PARK2 Mice knockout model

2.2 Invasive Treatments (S. Cheung)
  • 2.2.1 Deep Brain Stimulation (DBS)
    • 2.2.1a Deep Brain Stimulation in Parkinson’s Disease
    • 2.2.1b Patient Selection & Preparation
    • 2.2.1c Surgical Procedure & Outcomes
    • 2.2.1d Mechanisms
    • 2.2.1e Side effects and complications
  • 2.2.2 Ablative Methods
    • 2.2.2a Ablation in Parkinson’s Disease
    • 2.2.2b Comparing DBS and Pallidotomy

2.3 Pharmacological Agents and Stem Cell Therapy in PD Treatment (A. Son)
  • 2.3.1 L-DOPA
  • 2.3.2 MOA B Inhibitors
  • 2.3.3 Dopamine Agonists
  • 2.3.4 Non pharmacologic Management
  • 2.3.5 Embryonic Stem (ES) Cells
  • 2.3.6 Induced Pluripotential Stem (iPS) Cells
  • 2.3.7 Ethical Considerations and Controversies

3. Friedreich’s Ataxia (S. Farah)

3.1 Genetic Component:
  • 3.1.1 Inheritance pattern
  • 3.1.2 Cause of Friedreich's Ataxia
  • 3.1.3 Ways trinucleotide expansion can affect gene expression
    • 3.1.3a Blocking transcription elongation
    • 3.1.3b Aberrant Splicing
    • 3.1.3c Chromatin involvement in gene silencing
  • 3.1.4 Effect of transcription factors on FXN mRNA levels
3.2 Treatment
  • 3.2.1 Idebenone
  • 3.2.2 Histone deacetylase inhibitors

4. Prions (T. Dookhie) & (M. A. Rahman)

4.1 Introduction to prions
4.2 Proposed mechanisms of prion replication
  • 4.2a Prion hypothesis
  • 4.2b Nucleation dependent aggregation mechanism
  • 4.2c Cooperative autocatalysis model
  • 4.2d Heterodimer mechanism
Possible Functions
4.3 Cellular prions may promote neurogenesis and prolong survival
4.4 Cellular prions, anchored or not, may prevent neurodegeneration
  • 4.4a Results with a mutated PrPC compared to host encoded PrPC
  • 4.4b Soluble prion
4.5 PrPC may protect the brain in Amyotrophic Lateral Sclerosis
4.6 Human Transmissible Spongiform Encephalopathies
  • 4.6a Kuru

5.1 Prion-Like Properties of NDDs (M. A. Rahman)
  • 5.1 The Qualities That Make Prions Infectious
    • 5.1.1 Levels/Modes of infectivity
  • 5.2 Infectious Properties of Tau Protein
    • 5.2.1 Seeding Properties
    • 5.2.2 Transmission (Individual Level/Species Level)
  • 5.3 Infectious Properties of A-β Peptide
    • 5.3.1 Seeding and Self-Propagation Properties of A-β
  • 5.4 Infectious Properties of α-Synuclein
    • 5.4.1 Help of Gut Nervous System in PD Pathogenesis
  • 5.5 Possible Implication of an Infectious-theory of NDDs
    • 5.5.1 A Change in Thinking
    • 5.5.2 Potential Novel Treatments/Therapies


1. Lu B, Vogul H. Drosophila Models of Neurodegenerative Diseases, Annual Review of Pathology. (2009) 4:315-32.
2. Woulfe J. Nuclear bodies in neurodegenerative disease, Molecular Cell Research. (2008) 1783:2195-2206.
3. Doudet DJ. Neurodegenerative Disease, Molecular Imaging and Biology. (2007) 9:159-160.