Viral vector-based models of Parkinson's disease
Anke Van der Perren1, Chris Van den Haute, Veerle Baekelandt
1Katholieke Universiteit Leuven, Leuven, Belgium, Anke.VanderPerren@med.kuleuven.be.
Current Topics in Behavioral Neurosciences
|May 20, 2014
Summary
Developing advanced viral vector models, particularly those overexpressing alpha-synuclein, offers improved strategies for studying Parkinson's disease (PD) molecular pathways and testing novel therapeutics.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Animal models are crucial for understanding Parkinson's disease (PD) molecular mechanisms and developing treatments.
- Genetic models, utilizing PD-associated genes, are emerging as alternatives to toxin-induced models.
- Viral vector-mediated gene delivery is an effective method for targeting the central nervous system (CNS).
Purpose of the Study:
- To provide an overview of viral vector systems for CNS targeting.
- To describe existing viral vector-based PD models.
- To focus on alpha-synuclein overexpression models for PD research.
Main Methods:
- Review of various viral vector systems for CNS gene delivery.
- Description of genetic PD models based on gene overexpression (e.g., alpha-synuclein, LRRK2) and knockout/knockdown (e.g., parkin, DJ-1, PINK1).
- Emphasis on advancements in alpha-synuclein models using newer AAV serotypes and optimized vector technology.
Main Results:
- Viral vectors enable targeted gene expression in the CNS for PD modeling.
- Alpha-synuclein overexpression models are the most studied and prevalent.
- Third-generation alpha-synuclein models demonstrate enhanced face and predictive validity.
Conclusions:
- Advanced viral vector strategies, particularly for alpha-synuclein, are vital for PD research.
- Improved PD models enhance the reliability of therapeutic testing.
- These models hold promise for the development of novel Parkinson's disease therapies.
Related Concept Videos
01:24Parkinson Disease ll: Pathophysiology
26
Parkinson disease (PD) is a progressive neurodegenerative disorder primarily affecting movement, with additional non-motor features. Its pathophysiology involves complex interactions among genetic susceptibility, environmental exposures, and cellular dysfunction, including dopaminergic neuron loss, protein aggregation, and mitochondrial impairment.Selective NeurodegenerationA key feature is the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to reduced...
26
01:15Parkinson's Disease: Overview
2.2K
Neurodegenerative disorders are progressive diseases that cause irreversible damage and loss to neurons in specific brain areas. Examples of these disorders include Parkinson's disease, Alzheimer's disease, Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS). These disorders share characteristics such as proteinopathies, selective neuronal vulnerability, and a complex interplay between genetic and environmental factors. The primary therapeutic goal for these conditions is...
2.2K
01:21EPS and iPS Cells in Disease Research
3.2K
Embryonic and induced pluripotent stem cells are excellent models for disease research because of their ability to self-renew and differentiate into most cell types. Somatic cells from a patient are isolated and reprogrammed into induced pluripotent stem cells or iPSCs. These iPSCs are later differentiated into the desired cell type, which mirrors the diseased cell of the patient. In this way, disease models have been created for investigating diseases such as Down syndrome, type I diabetes,...
3.2K
01:24Parkinson Disease l: Introduction
28
Parkinson’s disease is a chronic, progressive neurodegenerative disorder that primarily affects movement. It is characterized by motor symptoms such as resting tremors, muscle rigidity, bradykinesia (slowness of movement), and postural instability. Patients may notice hand tremors at rest, stiffness during movement, or a shuffling gait. In addition to motor features, non-motor symptoms include sleep disturbances, mood and behavioral changes, constipation, and cognitive impairment, all of...
28
01:24Parkinson's Disease: Treatment
1.4K
Neurodegenerative disorders, such as Parkinson's Disease (PD), involve the gradual and irreversible destruction of neurons in particular brain areas. These disorders exhibit standard features like proteinopathies, selective vulnerability of some neurons, and an interaction of intrinsic properties, genetics, and environmental influences in neural injury.
Parkinson's Disease is primarily a result of the loss of dopaminergic neurons in the substantia nigra pars compacta. The cornerstone of...
Parkinson's Disease is primarily a result of the loss of dopaminergic neurons in the substantia nigra pars compacta. The cornerstone of...
1.4K