How the Targeting of Enzymes in Immune System can delay in Parkinsons’ Progression

Parkinson’s Disease (PD) is a long-term and age-related neurodegenerative disorder. Approximately 10 million people have PD worldwide. PD affects the central nervous system as the nerve cells in the brain don’t produce enough of dopamine. This causes impairment of the body’s motor functions. People with PD normally have symptoms that begin gradually, mostly on one side of the body. Subsequently, it affects both the sides.

PD usually arises in people above 60 years of age. It is chronic and progressive. Parkinson’s disease Pathogenesis shows that various environmental causes along with genetic risk factors contribute to its occurrence. Yet the exact causes are being investigated.

Parkinson’s Disease symptoms include - 

• Tremors in  hands, arms, legs, jaws and face
• Stiffness and rigidity  of the arms, legs and trunk
• Slowness of movement
• Poor balance and coordination

As symptoms worsen, PD patients may face trouble in walking, talking and even executing simple tasks. They may also experience other health issues like depression, sleep problems or difficulties in chewing, swallowing or speaking. Though PD has no permanent cure, a lot of research is going on slowing its progression.

Delaying Parkinson’s Progression by Targeting Enzymes in Immune System

Recent studies reveal that autoimmunity may have a role in the progression of PD. There is an enzyme called HDAC2 that is found in the immune cells of the brain. This enzyme regulates a crucial cellular mechanism known as epigenetics which controls the availability of certain genes. These genes are either read and translated into active proteins or silenced and hence made unavailable. According to the latest research, inhibiting the activity of this enzyme may prevent degeneration and death of nerve cells as seen in PD cases.

HDAC2 plays a key role in acting as potential therapeutic targets for several neurodegenerative diseases including PD. It is found that samples of microglia (immune cells) and dopamine-producing nerve cells in brain tissues collected from PD patients have high levels of HDAC2. This is in comparison to the corresponding levels in similar samples of healthy people.

It is interesting to note that HDAC2 levels correlated with the amount of LN3 (a marker of microglia activity) in PD samples. This is suggestive that HDAC2 may be linked to the greater pro-inflammatory and abnormal activity of microglia, when transitioning from protective brain cells to ones that attack and thereby damage healthy nerve cells.

Experimental cells replicating microglia behaviour also show increased levels of HDAC2 when pushed to a pro-inflammatory state. For quite some time now, it has been known that within pro-inflammatory environments microglia are responsible for the constant regulation and release of neurotoxin cytokines. Such environments are found in the substantia nigra in PD cases.

Thus the research findings support that HDAC2 may be specifically targeted and inhibited for reducing the effects of genes which cause neuroinflammation. Specifically, targeting HDAC2 gene expression levels in substantia nigra’s microglia can assist in reducing the progression of PD.

Latest medical innovations and evolving knowledge suggest various interventions and rehabilitation techniques for PD. This gives a new ray of new hope to patients living with this progressive neurological disease along with their families. PD is a complex disease that affects each individual differently. So PSP can help in deploying customized strategies and techniques applicable in daily life for coping up with PD limitations. PSP involves a comprehensive approach to the patient’s medical, functional and behavioural needs. This includes nursing care, nutritional counselling, rehabilitation techniques, speech and occupational therapies and fall -prevention measures.

PSP’s focus thus promotes independence and safety of PD patients for leading a better quality of life with lesser constraints.

Types of Exercises that should be a Part of a Parkinson's Patient's Life

Exercise, undeniably, plays a pivotal role in the life of those individuals who are affected by Parkinson's disease. It is not only good for their health, but also an essential factor that helps them to maintain body balance and enhance their mobility as Parkinson's is a Neurodegenerative disorder that causes severe mobility issues. 

According to a recent research conducted on Parkinson's disease revealed that daily exercise will help the individuals in mitigating the symptoms of Parkinson's disease at a greater level. Daily exercises reduce the stiffness and improve the mobility, posture and balance.  Here are few of the exercises that benefit the people with Parkinson's disease.

1. Exercises that Focus on Body Balance:
   Losing control over the limbs is one of the major issues Parkinson’s disease patients face. Simple exercises such as walking and stepping over minor obstacles help people in reducing the stiffness of their muscles and limbs. Few physical activities that involve in our regular life, such as climbing staircases will also help.
   
   
2. Strengthening Exercises:
   Strengthening Exercises, also known as 'Resistance exercise', help the individual to improve their muscle mass and rate of metabolism. Include physical activities such as squats, planks (only if your body supports) and jumping jacks on your exercise calendar.
   
   
3. Endurance Exercise:
   Endurance exercises such as jogging, cycling and swimming can benefit at a great level if practiced on a regular basis. These exercises improve the breathing pattern and cardiovascular functionality which indirectly helps in better oxygen reach to the brain.
   
   
4. Flexibility Exercises:
   Flexibility issues in Parkinson’s patients make the day to day life challenging. The elders will find it difficult even to perform simple physical activities such as sitting on or getting up from a chair, with Parkinson’s disease. Practicing yoga and tai chi every day will help in enhancing the body and limb flexibility.

Apart from these exercises, focus on physical activities such as dancing, aerobics and Jazzercise will help you in deriving the results in a faster way. Also, consider joining in yoga and meditation centers as mental Peace is as important as the regular exercises. Defensive arts such as Karate and Kung Fu will not only help you to improve your physical ability, but also motivates you to fight the Parkinson’s disease.

This is the very reason why few Parkinson's Support Agencies in the western countries encourage their patients to practice defensive art such as boxing and taekwondo with an objective to maintain the physical ability that is empowered with strong positive attitude.

Consistency is the key to derive the best results through these exercises. If performed on a regular basis, these exercises will start showing the results only after 3-6 months. Parkinson’s is tough and the only way to manage it effectively is by being tough on it.

Parkinson’s Disease – What You need to know about it?

Parkinson's disease is one of the most common neurodegenerative disorders that is mostly seen in the elderly citizens, usually after the age of sixty. It is a movement disorder that is caused by the incremental deterioration of motor function and muscle control due to loss of dopamine-produced by malfunctioning brain cells. Typical symptoms include trembling of the limbs and head while resting, stiffness, slowness, tremors, shuffling gait and impaired balance. With further progression, patients with Parkinson’s disease may experience difficulty to even walk, talk or execute simple chores. Other symptoms may include depression, dementia and anxiety.

Parkinson's Disease (PD) Stages

PD is a progressive ailment with multiple stages, each of which is characterized by typical patterns.

Early PD – Mild Symptoms

Stage 1

• Symptoms are mild and are usually mild and most likely affect only one side of the body  (unilateral involvement)
• Symptoms include tremor of one hand, rigidity, clumsy leg,  facial expression affected on one side

Stage 2

• Symptoms of PD are evident on both sides of the body (bilateral involvement) or at the midline
• Symptoms  are   loss of facial expression on both sides, decreased blinking, speech abnormalities, rigidity of muscles in the trunk

Mid Stage PD-Moderate Symptoms
Stage 3

• Symptoms of PD are characterized by loss of balance and slowness of movement
• Typical symptoms- Balance is compromised, inability to make the rapid, automatic and involuntary adjustments, all other symptoms of PD (as in previous stages) may also be present

Advanced PD

Stage 4

• Symptoms of PD are severely disabled
• Patients are noticeably incapacitated, though they may still be able to walk and stand without assistance. However, they are unable to lead an independent lifestyle completely and require help.

Stage 5

• Symptoms of PD are severe and are characterized by an inability to rise
• Patients are likely to fall when standing or turning and may freeze or stumble when walking.
• Hallucinations and delusions may also occur.

Treatment for PD
Treatment for PD varies from person to person depending upon their health condition and symptoms and may not involve a standardised procedure. It could include

• Medications for increasing the dopamine by simulating receptors in the brain, anti-depressants, anti-tremor drugs and cognition enhancing medications
• Surgical Therapy
• Lifestyle Modifications including regular exercise regimes and getting adequate rest.

Exercises for PD
Exercise and physical activity are a crucial component in the treatment of PD. It helps to maintain balance, improves mobility and aids in performing daily living chores. It should incorporate

• Stretching  exercises for increasing body flexibility
• Aerobic activities
• Exercises for strengthening and improving overall body resistance
• This can be achieved by exercises like biking, running, yoga, dancing, Pilates, weight training and non-contact boxing. The type of exercise chosen depends on existing symptoms and physical limitations. For instance, in sedentary people, merely getting up and doing small movements is beneficial. More physically fit patients may attempt regular and vigorous activities. Exercises also reduce non-motor symptoms such as depression or constipation.

Parkinson Support Program (PSP)
PD includes a broad spectrum of symptoms, including movement- and non-movement-related problems. Hence patients with PD may wish to work with a variety of Health Care Providers (HCP) apart from the specialist who primarily treats the disease.  Parkinson Support Program essentially provides individualized support to both PD patients and their caregivers by educating them about the disease, providing personalised support, making meaningful suggestions for better interactions with concerned physicians about the symptoms and progression and even connecting them with  the correct movement disorder specialist who treats PD. PSP also aids in seeking the help of allied services  like physical therapists for helping  address painful muscle stiffness or a counselor who can provide strategies for coping with depression in PD patients. It is important to have an early professional intervention with   occupational or speech therapists for preventing or delaying future limitations in PD. Thus PSP helps patients manage their functionality and maintain a safe environment despite disease progression.

Conclusion
The progression of PD and the degree to which the body is impaired varies depending upon the health condition of each individual.  However, with proper intervention and treatment, most patients can lead a long, self-reliant and productive life for many years to come.