MICROBIOTA INTESTINAL RELACIONADA A DOENÇA DE PARKINSON

RESUMO. A Doença de Parkinson é uma doença crônica, neurodegenerativa e progressiva onde não tem cura. Ainda há muitas investigações para se descobrir a causa da patologia. Em estudos recentes descobriram que pode ter uma relação direta com intestino, com a possibilidade de origem na microbiota intestinal e espalhando-se até o cérebro, com relação a uma desregulação no trato gastrointestinal. É reconhecido que, antes de aparecer os sinais e sintomas motores da doença, o organismo começa a sofrer alterações desde cedo, como a constipação intestinal, com o fortalecimento da hipótese de que a doença de Parkinson tenha início no trato gastrointestinal, e chegue até o cérebro através do nervo vago. Este trabalho pretende abordar sobre a microbiota intestinal e a sua conexão com a doença de Parkinson fazendo revisão de estudos e evidência de como sua composição no hospedeiro pode influenciar o seu metabolismo. A modulação da microbiota intestinal poderá, então, ser uma estratégia para o desenvolvimento de novas opções terapêuticas para o tratamento de doenças neurodegenerativas. ABSTRACT. Parkinson's Disease is a chronic, neurodegenerative and progressive disease that has no cure. There are still many investigations to discover the cause of the pathology. In recent studies they found that it may have a direct relationship with the intestine, with the possibility of originating in the intestinal microbiota and spreading to the brain, with respect to dysregulation in the gastrointestinal tract. It is recognized that, before the appearance of the motor signs and symptoms of the disease, the body begins to undergo changes from an early age, such as intestinal constipation, with the strengthening of the hypothesis that Parkinson's disease starts in the gastrointestinal tract and reaches the brain through the vagus nerve. This work intends to approach the intestinal microbiota and its connection with Parkinson's disease, reviewing studies and evidence on how its composition in the host can influence its metabolism. The modulation of the intestinal microbiota could then be a strategy for the development of new therapeutic options for the treatment of neurodegenerative diseases.

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Fractionally delineate the neuroprotective function of calbindin-D28k in Parkinson’s disease

International Journal of Biomathematics ◽

10.1142/s1793524518501036 ◽

2018 ◽

Vol 11 (08) ◽

pp. 1850103 ◽

Cited By ~ 5

Author(s):

Hardik Joshi ◽

Brajesh Kumar Jha

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Dimensional Space ◽

Cytosolic Calcium ◽

The Body ◽

Dopamine Neurons ◽

Reaction Diffusion Equation ◽

Substantia Nigra Pars Compacta ◽

Brain Disorder ◽

The Brain

Neuron is a fundamental unit of the brain, which is specialized to transmit information throughout the body through electrical and chemical signals. Calcium ([Formula: see text]) ions are known as second messengers which play important roles in the movement of the neurotransmitter. Calbindin-[Formula: see text] is a [Formula: see text] binding protein which is involved in regulation of intracellular [Formula: see text] ions and maintains [Formula: see text] homeostasis level, it also alters the cytosolic calcium concentration ([[Formula: see text]]) in nerve cells to keep the cell alive. Parkinson’s disease (PD) is a chronic progressive neurodegenerative brain disorder of the nervous system. Several regions of the brain indicate the hallmark of the PD. The symptoms of PD are plainly linked with the degeneration and death of dopamine neurons in the substantia nigra pars compacta located in midbrain which is accompanied by depletion in calbindin-[Formula: see text]. In the present paper, the neuroprotective role of calbindin-[Formula: see text] in the cytoplasmic [[Formula: see text]] distribution is studied. The elicitation in [[Formula: see text]] is due to the presence of low amount of calbindin-[Formula: see text] which can be portrayed and is a hallmark of PD. A one-dimensional space time fractional reaction diffusion equation is designed by keeping in mind the physiological condition taking place inside Parkinson’s brain. Computational results are performed in MATLAB.

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TLR2 and TLR4 in Parkinson’s disease pathogenesis: the environment takes a toll on the gut

Translational Neurodegeneration ◽

10.1186/s40035-021-00271-0 ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Anastazja M. Gorecki ◽

Chidozie C. Anyaegbu ◽

Ryan S. Anderton

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Nervous System ◽

Intestinal Barrier ◽

The Body ◽

Enteric Neurons ◽

Gut Dysfunction ◽

Gut Homeostasis ◽

The Brain

AbstractParkinson’s disease (PD) is an incurable, devastating disorder that is characterized by pathological protein aggregation and neurodegeneration in the substantia nigra. In recent years, growing evidence has implicated the gut environment and the gut-brain axis in the pathogenesis and progression of PD, especially in a subset of people who exhibit prodromal gastrointestinal dysfunction. Specifically, perturbations of gut homeostasis are hypothesized to contribute to α-synuclein aggregation in enteric neurons, which may spread to the brain over decades and eventually result in the characteristic central nervous system manifestations of PD, including neurodegeneration and motor impairments. However, the mechanisms linking gut disturbances and α-synuclein aggregation are still unclear. A plethora of research indicates that toll-like receptors (TLRs), especially TLR2 and TLR4, are critical mediators of gut homeostasis. Alongside their established role in innate immunity throughout the body, studies are increasingly demonstrating that TLR2 and TLR4 signalling shapes the development and function of the gut and the enteric nervous system. Notably, TLR2 and TLR4 are dysregulated in patients with PD, and may thus be central to early gut dysfunction in PD. To better understand the putative contribution of intestinal TLR2 and TLR4 dysfunction to early α-synuclein aggregation and PD, we critically discuss the role of TLR2 and TLR4 in normal gut function as well as evidence for altered TLR2 and TLR4 signalling in PD, by reviewing clinical, animal model and in vitro research. Growing evidence on the immunological aetiology of α-synuclein aggregation is also discussed, with a focus on the interactions of α-synuclein with TLR2 and TLR4. We propose a conceptual model of PD pathogenesis in which microbial dysbiosis alters the permeability of the intestinal barrier as well as TLR2 and TLR4 signalling, ultimately leading to a positive feedback loop of chronic gut dysfunction promoting α-synuclein aggregation in enteric and vagal neurons. In turn, α-synuclein aggregates may then migrate to the brain via peripheral nerves, such as the vagal nerve, to contribute to neuroinflammation and neurodegeneration typically associated with PD.

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Epigenetic inactivation of the autophagy–lysosomal system in appendix in Parkinson’s disease

Nature Communications ◽

10.1038/s41467-021-25474-x ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Juozas Gordevicius ◽

Peipei Li ◽

Lee L. Marshall ◽

Bryan A. Killinger ◽

Sean Lang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Dna Methylation ◽

Parkinson's Disease ◽

Gastrointestinal Tract ◽

Aberrant Methylation ◽

Epigenetic Alterations ◽

Potential Mechanism ◽

Lysosomal System ◽

A Site ◽

The Brain

AbstractThe gastrointestinal tract may be a site of origin for α-synuclein pathology in idiopathic Parkinson’s disease (PD). Disruption of the autophagy-lysosome pathway (ALP) may contribute to α-synuclein aggregation. Here we examined epigenetic alterations in the ALP in the appendix by deep sequencing DNA methylation at 521 ALP genes. We identified aberrant methylation at 928 cytosines affecting 326 ALP genes in the appendix of individuals with PD and widespread hypermethylation that is also seen in the brain of individuals with PD. In mice, we find that DNA methylation changes at ALP genes induced by chronic gut inflammation are greatly exacerbated by α-synuclein pathology. DNA methylation changes at ALP genes induced by synucleinopathy are associated with the ALP abnormalities observed in the appendix of individuals with PD specifically involving lysosomal genes. Our work identifies epigenetic dysregulation of the ALP which may suggest a potential mechanism for accumulation of α-synuclein pathology in idiopathic PD.

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Which Drug for Parkinsonism? Walking, Stiffness, Tremor, and Slowness

Dementia with Lewy Body and Parkinson's Disease Patients ◽

10.1093/oso/9780199977567.003.0011 ◽

2013 ◽

Author(s):

J. Eric Ahlskog

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Basal Ganglia ◽

Substantia Nigra ◽

The Body ◽

Brain Dopamine ◽

Arm Swing ◽

Repetitive Movements ◽

The Brain ◽

Repetitive Motor

In Chapters 1 and 4, we briefly summarized the symptoms of parkinsonism. Parkinsonism implies movement problems that are typical of Parkinson’s disease. They remain treatment issues during the lifetime of people with Parkinson’s disease, even if dementia develops. Similarly, parkinsonism also typically occurs in DLB, although to variable degrees. In these disorders parkinsonism primarily reflects low brain dopamine levels and improves with dopamine replacement therapy, often markedly. Parkinsonism occurs when a region of the brain called the basal ganglia ceases to work properly (see Figure 4.2 in Chapter 4). As discussed in Chapter 4, the substantia nigra is a crucial regulator of basal ganglia activity, which is mediated by dopamine release in the striatum. The substantia nigra degenerates in these Lewy disorders and, as a result, brain dopamine declines. With a decline in dopamine, movement slows. Bradykinesia is the medical term for such slowness. This manifests as not only slowed movement but also less movement and smaller than normal movements. Unconscious automatic movements, such as blinking or arm swing, diminish. A unique tremor of the hands (sometimes legs) often develops when these limbs are in a relaxed position (rest tremor). For unknown reasons, the brain is not affected symmetrically, hence, neither is the body. Typically, one side of the body is much more impaired than the other. The extent to which these symptoms develop differs from person to person and includes various combinations of the following components. The slowness may be apparent on one or both sides of the body. For example, one leg may lag behind when walking. The overall appearance is characterized by moving much slower than expected for one’s age. The person feels as if they are moving in molasses—everything slows down. Many of our daily activities involve repeated small movements, such as writing or brushing teeth. In the Lewy conditions of DLB and PDD, the size (amplitude) of repetitive movements diminishes, impairing the activity. This is exemplified by the small handwriting of someone with parkinsonism, termed micrographia. Clinicians assess repetitive motor function by asking the patient to repetitively tap the thumb and index finger.

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Physical therapy of the early non-motorized violations to slow the progression of Parkinson's disease

Likarska sprava ◽

10.31640/jvd.1-2.2019(17) ◽

2019 ◽

pp. 117-120

Author(s):

А. I. Labinskiy ◽

G. B. Labinska

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Physical Therapy ◽

The Body ◽

Motor Symptoms ◽

Physical Treatment ◽

Treatment Regimens ◽

Objective State ◽

Non Motor Symptoms ◽

The Brain

The authors developed and applied the original complex of innovative combined physical therapy of non-motor manifestations of the early stages of Parkinson's disease to slow its progression. Applied concomitant treatments affect some parts of the etiology and pathogenesis of non-motor manifestations of Parkinson's disease. In particular, hirudotherapy restores the rheological properties of blood without side effects characteristic of known anticoagulants; helps to restore tissue trophism, in particular the brain. Nutritional correction prevents the development of digestive disorders. The main principles of such nutrition were: 1. The role of antioxidant saturation of the diet for the correction of metabolism. 2. The value of increasing the number of "ballasts" in the diet. 3. "Free mode" of food intake (at the request of the organism), taking into account the human biorhythms (daily, seasonal and psychological). 4. The need for periodic short-term fasting - as a method of cleansing the body. 5. The need for separate power. Manual therapy in the variant proposed by the authors prevents the vertebral component of the destructive processes in the brain. After the use of combined physical therapy, an improvement in the objective state of patients with Parkinson's disease was noted. According to the study, non-motor symptoms on the scale of autonomic disorders and non-motor symptoms (NMSS) were statistically significantly less pronounced in all patients examined in the group of patients using the developed complex of physical therapy compared to the group of patients without using the developed complex of physical therapy. Considering the improvement of the objective state of patients after the applied physical treatment, we can recommend the indicated therapeutic technique for the complex treatment of early non-motor manifestations of Parkinson's disease, slowing its progression and improving the effectiveness of existing modern treatment regimens of the studied pathology.

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Management of Symptoms of Parkinsonism Through Panchakarma Therapy

10.31219/osf.io/a3m8n ◽

2020 ◽

Author(s):

Ashok Kumar Pandey ◽

Saurabh Mishra ◽

Alka Mishra

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Neurodegenerative Disorder ◽

Herbal Medicines ◽

The Elderly ◽

The Body ◽

Lower Back ◽

Patient Reported ◽

The Brain

Background: Parkinson's disease is a disabling neurodegenerative disorder, mainly affecting the elderly population. Symptoms of Parkinsonism include motor function abnormalities, tremors in hands and legs, postural instability, etc. Side-effect free, long-term management of Parkinsonism is still a challenge. According to Ayurveda, the disease that resembles the symptoms associated with Parkinson's disease is Kampavata (kampa means tremors), which is primarily caused by the imbalance of the Vata Dosha. Various Panchakarma procedures have been found useful in the treatment of different Vata Vyadhis (diseases caused by the imbalance of Vata Dosha).Methodology: Panchakarma therapy was administered for 19 days to a male patient suffering from symptoms of Parkinsonism (Kampavata) since about nine months, as well as other associated ailments. According to Ayurveda, Kampavata is primarily associated with Vata imbalance. Hence, Vata pacifying herbal medicines, that also provide strengthening and nourishing effect to the degenerative tissues of the body, as well as nourishment to the brain, were used.Results: The patient experienced significant relief in the tremors in B/L hands, numbness in B/L big toes, weakness in lower extremity, and lower back pain. The patient also experienced notable relief in the complaints of Constipation, Gastric upset, and Flatus. Overall, the patient reported a satisfactory experience after taking the therapy.Conclusion: Panchakarma therapy showed encouraging results in the management of symptoms associated with Parkinsonism, as well as other associated ailments, in short duration of time.

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The Stand-Alone Tremor

10.1093/med/9780190607555.003.0022 ◽

2016 ◽

Author(s):

Robertus M. A. de Bie

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Head And Neck ◽

Essential Tremor ◽

Progressive Disease ◽

The Body ◽

Head Tremor ◽

Kinetic Tremor ◽

The Voice

Essential tremor is defined as long-standing bilateral hand/arm tremor that is visible and may occur persistently during posture-holding, simple movements, and action. The tremor may be slightly asymmetrical. Other areas of the body that may be affected are head and neck (most frequently), the voice, and legs. Head tremor without limb tremor is accepted as essential tremor, although this definition remains controversial. Essential tremor is a progressive disease and manifests at any age. Tremor in Parkinson’s disease mostly starts unilaterally. A no–no or yes–yes tremor of the head indicates essential tremor, whereas a tremor of the jaw or tongue fits with Parkinson’s disease. The cogwheel phenomenon may also occur in patients with essential tremor. Toxins and medications as the cause for postural/kinetic tremor must be ruled out. Pharmacological options for essential tremor can be unsatisfactory.

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Minireview on the Relations between Gut Microflora and Parkinson’s Disease: Further Biochemical (Oxidative Stress), Inflammatory, and Neurological Particularities

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/4518023 ◽

2020 ◽

Vol 2020 ◽

pp. 1-15 ◽

Cited By ~ 5

Author(s):

Ovidiu-Dumitru Ilie ◽

Alin Ciobica ◽

Jack McKenna ◽

Bogdan Doroftei ◽

Ioannis Mavroudis

Keyword(s):

Oxidative Stress ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Gastrointestinal Tract ◽

Gastrointestinal Symptoms ◽

Progressive Increase ◽

Signalling Pathways ◽

Gut Microflora ◽

Number Of Patients ◽

The Brain

The aetiology of Parkinson’s disease (PD) is a highly debated topic. Despite the progressive increase in the number of patients diagnosed with PD over the last couple of decades, the causes remain largely unknown. This report is aimed at highlighting the main features of the microbial communities which have been termed “the second brain” that may be a major participant in the etiopathophysiology of PD. It is possible that dysbiosis could be caused by an overactivity of proinflammatory cytokines which act on the gastrointestinal tract as well as infections. The majority of patients who are diagnosed with PD display gastrointestinal symptoms as one of the earliest features. In addition, an unbalanced cycle of oxidative stress caused by dysbacteriosis may have the effect of gradually promoting PD’s specific phenotype. Thus, it seems that bacteria possess the ability to manipulate the brain by initiating specific responses, defining their capability to configure the human body, with oxidative stress playing a pivotal role in preventing infections but also in activating related signalling pathways.

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DEMONSTRATION OF PRECISE RELATIONSHIPS AND LINKS BETWEEN TYPE 2 DIABETES MELLITUS, INSULIN RESISTANCE AND PARKINSON’S DISEASE

International Journal of Research -GRANTHAALAYAH ◽

10.29121/granthaalayah.v7.i12.2019.320 ◽

2020 ◽

Vol 7 (12) ◽

pp. 259-270

Author(s):

Habib ur Rehman ◽

Kaleemullah ◽

Abdul Malik Tareen

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Type 2 Diabetes Mellitus ◽

The Body ◽

Diabetic Patients ◽

The Brain

Diabetes is a metabolic disorder that intessssrferes with the body's ability to consume food and convert it into energy. The most common mode of diabetes in type 2 diabetes mellitus (T2DM) is that the body cannot effectively use insulin produced by the pancreas. This is called insulin resistance. Parkinson's Disease (PD) is a chronic neurodegenerative motor defect whose properties work is hindrance with locomotion. This is due to the loss of neurons in the substantia nigra area under the brain that produces dopamine, a chemical messenger that transmits signals that produce smooth, meaningful movement. Dopamine loss caused by neuronal damage and death causes impaired movement. Cells rely on glucose for energy, and insulin helps to convert glucose into energy. In both Parkinson's disease and type 2 diabetes, changes in the brain can result in signaling interruptions that affect normal functioning. Insulin resistance also reaches the brain and produces severe changes in the nerve cells, increasing the risk of Parkinson's disease and abnormally promoting high blood sugar leads to high-rise the inflammation, associated with the development of Parkinson's disease. Diabetes suffering peoples are more likely to have Parkinson's disease. Parkinson's disease is 32% higher in people with type 2 diabetes than in non-diabetic patients. Patients with type 2 diabetes along with its complication have a 49% higher risk of Parkinson’s disease, while those having only type 2 diabetes without complications have a 30% risk of parkinson’s disease. In particular, younger patients with diabetes (25 to 44 years of age) have an approximately fourfold increased risk of developing Parkinson's compared with adults of similar age without diabetes. Researchers has estimated the high risk of developing PD based on longitudinal data methodology for people with type 2 diabetes. Initial studies have reported more than 400 genes linked in both conditions. The potential link between type 2 diabetes and Parkinson's disease has been the topic of medical dialogue and scientific research for years. Recently, animal and in vitro studies have shown that the pathophysiology and clinical symptoms of Parkinson's disease are concerned more with insulin dysregulation and changes in insulin action.

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Transcranial parenhymal sonography in the diagnosis of Parkinson's disease

Vojnosanitetski pregled ◽

10.2298/vsp0808601m ◽

2008 ◽

Vol 65 (8) ◽

pp. 601-605 ◽

Cited By ~ 5

Author(s):

Milija Mijajlovic ◽

Igor Petrovic ◽

Tanja Stojkovic ◽

Marina Svetel ◽

Elka Stefanova ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Dynamic Range ◽

Brain Structures ◽

Transcranial Sonography ◽

The Body ◽

Characteristic Finding ◽

Phased Array Ultrasound ◽

Array Ultrasound ◽

The Brain

Bacground/Aim. Modern ultrasound systems allow highresolution transcranial sonography (TCS) of the brain structures. Enlargement of the echogenic signal (hyperechogenicity) of the substantia nigra (SN) has been reported as a highly characteristic finding in idiopathic Parkinson's disease (PD) and is thought to reflect increased amounts of iron, bound to proteins other than ferritin, in the SN in the course of neurodegeneration. The aim of our study was to investigate the prevalence of the SN hyperechogenicity in PD patients, as well as its possible clinical correlates. Methods. The study comprised 103 consecutive PD patients and 50 healthy age-matched controls. For TCS examination a color-coded, phased array ultrasound system equipped with a 2.5 MHz transducer was used (ESAOTE Technos MP, Italia). The examination was performed through a preauricular acoustic bone window with a penetration depth of 16 cm and a dynamic range of 45-50 dB. The SN was identified within the butterfly shaped structure of the mesencephalic brainstem, with scanning from both temporal windows. Results. The SN hyperechogenicity was identified in 95 out of 103 examined PD patients (92%), which was marked in 60 (63%), and moderate in 35 patients (37%). Median SN echogenic size was larger contralateral to the clinically more affected side of the body. Unilateral SN hyperechogenicity was also found in 5 out of 50 healthy controls (10%). No ventricular enlargements were notified in our study. Conclusion. Our study demonstrated SN hyperechogenicity in more than 90% of PD patients. In adult subjects without neurological symptoms, the TCS finding of at least unilaterally marked SN hyperechogenicity indicates a subclinical functional impairment of the nigrostriatal dopaminergic system. .

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