Leucine-Rich Repeat Kinase 2 : An Analysis Of Parkinson's Disease

Identified as LRRK2, this gene mutation only accounts for one to two percent of all cases of Parkinson’s disease. (Michael J. Fox Foundation)

When a teenager at our clinic was diagnosed with Juvenile Parkinsonism (JP) our challenge as physical therapists started with performing different evaluation tools to produce an assertive assessment. Because JP is so rare most of the times it gets confused with other conditions. Juvenile Parkinsonism is associated with high - Parkinson’s risk genetic mutations or environmental toxin exposure (Pan-Mantojo & Reichman, 2014). 65% of people under 20 years of age with JP is due to a genetic mutation (Thomsen & Rodnitzky, 2010). Having the Leucine - rich repeat kinase 2 (LRRK-2) and/or parkin9 genes increases the possibility of developing JP. It is important the entire team treating patients with juvenile PD onset get embedded in the condition in order to provide the best care possible.

Parkinson Disease’s (PD) is defined as progressive loss of pigmented neurons or cells in the substantia nigra of the brain. These cells manufacture the molecule dopamine, a chemical responsible for regulating purposeful movements. Moreover, when the dopamine level in the brain depletes by 80 percent, the patient will begin experiencing symptoms of PD. Genetics also play a vital role in Parkinson’s development--mutations in the Leucine-Repeat Kinase 2 are its greatest contributors. Furthermore, dopamine levels progressively drop in patients with the disease; therefore, their symptoms gradually become severe as they age. Parkinson’s symptoms are categorized into primary, secondary, motor, and nonmotor. (Fallon & Cataldo, 2013)

Parkinson's disease (PD) is an adult-onset neurodegenerative disorder, concomitant with neuronal loss predominantly in the substantia nigra pars compacta (SNpc) and inclusions comprising of the synaptic protein, α-synuclein (α-syn). Recent developments have advanced our understanding on the multitude of inter-mingled deleterious factors contributing to PD neuropathological aetiologies. These encompass “cell autonomous” processes, for instance, autophagy, and mitochondrial dysfunction, and “non-cell autonomous” processes, which embrace trans-synaptic transmission of abnormal proteins and neuro-inflammation (Foltynie and Kahan; 2012). Although the “prion-like” nature of pathological α-syn is a theme of intense research

Parkinson’s disease (PD) is a progressive disorder of unknown etiology that has no cure. It is characterized by bradykinesia, rest tremor, cogwheel rigidity and postural instability, along with a number of non-motor signs. The neurochemical hallmark of PD is dopamine loss in the nigrostriatal dopamine system (Adler, 2011). In the substantia nigra (SN) of people with PD there is a loss of neuronal cells, demonstrated by the degeneration of brainstem nuclei (Brooks, 1998). This typically shows as Lewy bodies – spherical masses of protein that develop inside nerve cells. However the progression of neuronal loss is quite variable in different PD patients and at different phases of the disease. At present there is no treatment that affects the degeneration, for example by slowing the rate of cell death or by protecting neurons.

Kinase activity of mutant LRRK2 has been shown to mediate neuronal toxicity and cell death in PD (Smith et al., 2006). The BRAF kinase which is believed to cause a significant proportion of melanoma is similar to the kinase domain of LRRK2, which is known to drive a significant proportion of malignant melanoma (Bishop et al., 2009; Flaherty et al., 2010; Flemming et al., 2010; Paisan Ruiz et al., 2010; Shen J et al., 2004), implying that there could be functional analogies between the activation of the BRAF kinase in melanoma and activation of LRRK2 kinase in PD-associated neurodegeneration (Paisn-Ruiz et al., 2010)

Living with Parkinson’s disease can be very arduous, it demands a lot of treatment and can be very hard to cope with. Parkinson’s disease can be caused by genetics, environmental triggers, like certain toxins, the presence of Lewy bodies and lastly the presence of alpha-syncuclein found within the Lewy bodies. Lewy bodies are indicators or markers of Parkinson’s disease in the brain and if a-synuclein

Parkinson’s disease (PD) is a neurodegenerative debilitating movement disease which gets worse over time (Medscape, 2015). After much research and study no known cause has yet been determined and experts have hypothesized that it is a mix of inherited and environmental factors (Medscape, 2015). However, regardless of the unspecific cause, it is characterized by a significant loss in dopamine transportation to the basal ganglia which manifests itself in the three following physiologic signs: resting tremor, rigidity and bradykinesia (slow and reduced movement) (Mahan, Escott-Stump & Raymond, 2012). In North America PD is one of the most prevalent neurological disorders affecting relatively 1% of persons older than 65 years of age and within 5 years 66% of patients are disabled and by 10 years 80% are disabled (Mahan et al., 2012). PD increases in incidence with age, is not partial to socioeconomic status, is more common in whites than in Asian or Blacks and is predominately seen between the ages of 40 and 70 (Mahan et al., 2012).

Parkinson’s disease (PD) is a chronic, progressive neurodegenerative disorder affecting approximately 1% of the population over age 60 [1]. It is the second most common neurodegenerative disorder after Alzheimer's disease and is predicted to increase in prevalence as the population ages, imposing a social and economic burden on society [2]. PD is classically characterized by a loss of mesencephalic dopaminergic neurons and the development of Lewy Bodies within the substantia nigra pars compacta (SNpc) [3]. Neurons originating in the SNpc project to the striatum where they activate D1 or D2 receptors to stimulate the direct or indirect pathway of the basal ganglia, respectively. Activation of the direct pathway by dopamine (DA) results in

Parkinson’s disease (PD) is a neurodegenerative disease which is progressive, incurable and debilitating. The disease is caused by a loss of dopamine producing neurons in the brainstem which leads primarily to motor deficits. In Australia, 1 in 350 people live with PD and the prevalence is quickly growing (Parkinson 's Queensland, 2014). While most of the people diagnosed with PD are over 65 years old, people as young as 30 can develop the condition (Parkinson 's Queensland, 2014). Currently, there is no known cure for the disease and thus treatment options are limited, meaning that those living with PD, will have to manage the condition for the rest of their life.

Parkinson’s disease (PD) is an incurable, progressive movement disorder affecting approximately one million Americans (www.pdf.org) and is the 14th leading cause of death in the US (www.cdc.gov). The pathogenesis of PD involves the degeneration of neurons, especially dopaminergic neurons in the substantia nigra of the midbrain [1], and the presence of Lewy bodies/neuritis in various brain regions [2]. Deficiency of the nigro-striatal pathways can cause dopamine depletion-specific symptoms such as motor dysfunctions and multiple non-motor clinical issues. The clinical diagnosis of PD is based on the four cardinal symptoms: tremor, rigidity, bradykinesia, and postural instability [3], which are delayed and subtle. Since the

Parkinson’s disease is a disease that affects the nervous system. Some common symptoms of Parkinson’s disease are tremors, slowed movement, impaired posture and balance, and speech changes. These phenotypes that are expressed in humans with Parkinson’s disease are also expressed in mice. Mice have a nervous system that is comparable to a human’s nervous system. In this experiment, mice will be exposed to radiation and the new phenotypes will be observed to determine the causes of Parkinson’s disease as well as the gene location for the mutation using forward genetic screening methods. If a mouse exhibits these symptoms stated above, then it is likely that they are a carrier of Parkinson’s disease, which will be passed onto the next generation.

Parkinson’s disease (PD) is a progressive and chronic neurodegenerative disorder. It can be characterised clinically by tremor development, bradykinesia, and rigidity (Chaturvedi, 2008). PD is pathologically caused by the loss of dopaminergic neurons in the substantia pars compacta, which regulates motor control, (Magdalena Guerra-Crespo, 2011) with a degeneration of the neurotransmitter dopamine (Wood & Calne, 2011). This disturbance in the movement control centre also decline the presence of laminated inclusions (Lewy bodies) clumped abnormally by protein gene called alpha-synuclein that links to the development of both sporadic, and hereditary cases of PD (Michael J. Fox Foundation, 2012). Both genetic and environmental elements play a role

The rat model is also used extensively in research and used as a model to study the pathogenesis of Parkinson’s disease. Rat models have a number of advantages over that of the mouse model. The rat is bigger in size, meaning larger tissue samples e.g. when examining the brain for survival of iPSC derived neural cells, easier to handle as its more docile than mice, rats’ physiology is closer to humans than that of mice and rats are more intelligent than mice with richer behaviour, making them more suitable in behavioural assays

Indisputable evidence has proven that oxidative stress and radical oxygen system is one of the major factors that contributes to neuronal loss in several neurodegenerative disorders including Parkinson disease. Despite the advances in medical sciences and several studies which have centered on understanding the pathogenesis and mechanism involved in Parkinson disease, not much research in understanding the intricacy of the pathophysiology of the