LRRK2 mouse models: dissecting the behavior, striatal neurochemistry and neurophysiology of PD pathogenesis

2017 ◽  
Vol 45 (1) ◽  
pp. 113-122 ◽  
Author(s):  
Mattia Volta ◽  
Heather Melrose
Keyword(s):  
Mouse Models ◽  
Animal Behavior ◽  
Research Question ◽  
Critical Approach ◽  
Drug Effectiveness ◽  
Disease Mechanisms ◽  
Mouse Modeling ◽  
Familial Parkinson’S Disease ◽  
Neuroprotective Therapies ◽  
Genetic Mouse Models

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of familial Parkinson's disease (PD), resembling the sporadic disorder. Intensive effort has been directed toward LRRK2 mouse modeling and investigation, aimed at reproducing the human disease to inform mechanistic studies of pathogenesis and design of neuroprotective therapies. The physiological function of LRRK2 is still under exploration, but a clear role in striatal neurophysiology and animal behavior has emerged. Alterations in LRRK2 impair dopamine (DA) transmission, regulation and signaling, in addition to corticostriatal synaptic plasticity. Consistently, several subtle abnormalities in motor and nonmotor abilities have been demonstrated in LRRK2 genetic mouse models, generally paralleling preclinical symptoms of early DA dysfunction. However, the variability in model design and phenotypes observed requires a critical approach in interpreting the results, adapting the model used to the specific research question. Etiologically appropriate knockin mice might represent the ultimate animal model in which to study early disease mechanisms and therapies as well as to investigate drug effectiveness and off-target consequences.

scholarly journals Modeling Rare Human Disorders in Mice: The Finnish Disease Heritage

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3158
Author(s):  
Tomáš Zárybnický ◽  
Anne Heikkinen ◽  
Salla M. Kangas ◽  
Marika Karikoski ◽  
Guillermo Antonio Martínez-Nieto ◽  
...  
Keyword(s):  
Human Physiology ◽  
Animal Models ◽  
Mouse Models ◽  
Rare Diseases ◽  
Disease Modeling ◽  
Common Disease ◽  
Molecular Pathways ◽  
Finnish Population ◽  
Disease Mechanisms ◽  
Human Disorders

The modification of genes in animal models has evidently and comprehensively improved our knowledge on proteins and signaling pathways in human physiology and pathology. In this review, we discuss almost 40 monogenic rare diseases that are enriched in the Finnish population and defined as the Finnish disease heritage (FDH). We will highlight how gene-modified mouse models have greatly facilitated the understanding of the pathological manifestations of these diseases and how some of the diseases still lack proper models. We urge the establishment of subsequent international consortiums to cooperatively plan and carry out future human disease modeling strategies. Detailed information on disease mechanisms brings along broader understanding of the molecular pathways they act along both parallel and transverse to the proteins affected in rare diseases, therefore also aiding understanding of common disease pathologies.

scholarly journals Integration Level of Social Environmental Disclosure (SED) Between The Global Reporting Initiative(GRI)- Sustainability Reporting and The International Integrated Reporting Council (IIRC) Reporting Among European Companies

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Suzila Mohamed Yusof ◽  
Nazaria Md Aris ◽  
Nurul Syuhada Zaidi
Keyword(s):  
Business Strategy ◽  
Research Question ◽  
Sustainability Reporting ◽  
Global Reporting Initiative ◽  
Critical Approach ◽  
Integrated Reporting ◽  
Environmental Disclosure ◽  
Social And Environmental Disclosure ◽  
Social Environmental ◽  
International Integrated Reporting Council

This critical approach study examines the social and environmental disclosure (SED) between Sustainability Reporting (SR) and Integrated Reporting (IR) among European companies. The research question is to examine the integration level of SED within SR and IR. Applying the critical text analysis method, the GRI G3 guidelines were used to examine a sample of ten European companies. The reports for the selected companies must incorporate fully applied IR without producing any more SR in order to analyse the validity of the data. This study has discovered that there is less integration of SED in IR than SR. It is apparent that the IR approach is more towards the primary groups (investors) rather than other stakeholders, society and the environment as a whole. Hence, IR is only a mirror of sustainability for business strategy. Therefore, IR needs to engage reports with other stakeholders to sustain long-term growth.

Functional genetic mouse models: promising tools for investigation of the proteolytic internet

2009 ◽  
Vol 390 (2) ◽  
pp. 91-97 ◽  
Author(s):  
Achim Krüger
Keyword(s):  
Mouse Models ◽  
Knockout Mice ◽  
Gold Standard ◽  
Disease Susceptibility ◽  
Molecular Polymorphism ◽  
Specific Protease ◽  
Molecular Phenotypes ◽  
The Impact ◽  
Genetic Mouse Models

Abstract Knockout mice are the gold standard to probe for the role of a specific protease within the interacting network of proteases, substrates, and inhibitors. This proteolytic network, or protease web, determines cell signaling and organ homeostasis. Therefore, protease deficiency or inhibition is intrinsically tied to alterations within this network, always leading to new molecular phenotypes, which define susceptibility of an organ to disease. Furthermore, recent hints, mainly from research on matrix metalloproteinases, about the impact of the protease web on inter-organ signaling molecules suggest the existence of a proteolytic internet of communicating local organ- or molecular polymorphism-specific networks, thereby defining homeostasis and disease susceptibility in the whole organism.

Behavioral phenotypes and pharmacology in genetic mouse models of Parkinsonism

2006 ◽  
Vol 17 (5-6) ◽  
pp. 383-391 ◽  
Author(s):  
Sheila M. Fleming ◽  
Marie-Fran??oise Chesselet
Keyword(s):  
Mouse Models ◽  
Behavioral Phenotypes ◽  
Genetic Mouse Models
Sign in / Sign up

Export Citation Format

Share Document