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International Journal of Molecular... Mar 2021Parkinson's disease (PD) is a neurodegenerative disorder that manifests with rest tremor, muscle rigidity and movement disturbances. At the microscopic level it is... (Review)
Review
Parkinson's disease (PD) is a neurodegenerative disorder that manifests with rest tremor, muscle rigidity and movement disturbances. At the microscopic level it is characterized by formation of specific intraneuronal inclusions, called Lewy bodies (LBs), and by a progressive loss of dopaminergic neurons in the striatum and substantia nigra. All living cells, among them neurons, rely on Ca as a universal carrier of extracellular and intracellular signals that can initiate and control various cellular processes. Disturbances in Ca homeostasis and dysfunction of Ca signaling pathways may have serious consequences on cells and even result in cell death. Dopaminergic neurons are particularly sensitive to any changes in intracellular Ca level. The best known and studied Ca sensor in eukaryotic cells is calmodulin. Calmodulin binds Ca with high affinity and regulates the activity of a plethora of proteins. In the brain, calmodulin and its binding proteins play a crucial role in regulation of the activity of synaptic proteins and in the maintenance of neuronal plasticity. Thus, any changes in activity of these proteins might be linked to the development and progression of neurodegenerative disorders including PD. This review aims to summarize published results regarding the role of calmodulin and its binding proteins in pathology and pathogenesis of PD.
Topics: Animals; Calcium Signaling; Calmodulin; Homeostasis; Humans; Parkinson Disease; Protein Binding; Substrate Specificity
PubMed: 33809535
DOI: 10.3390/ijms22063016 -
Anesthesiology and Pain Medicine Feb 2023Neuromuscular diseases (NMDs) are regarded as a clinically and genetically heterogeneous group of diseases characterized by weakening muscle strength and dystrophic... (Review)
Review
CONTEXT
Neuromuscular diseases (NMDs) are regarded as a clinically and genetically heterogeneous group of diseases characterized by weakening muscle strength and dystrophic changes in the muscle. Due to the nature of these diseases, it can be challenging for anesthesiologists to provide appropriate pain medications, symptom management, and other necessary techniques that are implemented to anesthetize the patient properly.
EVIDENCE ACQUISITION
This study was based on the available literature and the authors' experience. The current study aimed to review the available anesthesia for patients suffering from NMDs. The search process resulted in the detection of relevant articles using valid keywords on electronic databases, including Embase, PubMed, Scopus, Web of Science, and Cochrane Library. Subsequently, 19 articles published between 2009 to 2022 were identified as eligible for this review.
RESULTS
When anesthetizing a patient with NMD, special attention should be paid to preoperative evaluation, medical-history taking, risk of difficult intubation or cardiac incidents, respiratory insufficiency, and frequent pulmonary infections. It is also necessary to keep in mind that these patients are at risk of prolonged paralysis, hyperkalemia, rigidity, malignant hyperthermia, cardiac arrest, rhabdomyolysis, or even death.
CONCLUSIONS
Problems of anesthesia in patients with NMDs arise from the nature of the condition itself and the interaction of anesthetics and muscle relaxants with anticholinesterase drugs used in therapy. Each patient's individual risk should be assessed before anesthesia. Therefore, it is important (and even necessary before major surgery) to perform a thorough preoperative examination to not only determine perioperative risk but also to ensure optimal perioperative follow-up.
PubMed: 37409004
DOI: 10.5812/aapm-132088 -
Nucleus (Austin, Tex.) Dec 2020Nuclear lamins form an elastic meshwork underlying the inner nuclear membrane and provide mechanical rigidity to the nucleus and maintain shape. Lamins also maintain... (Review)
Review
Nuclear lamins form an elastic meshwork underlying the inner nuclear membrane and provide mechanical rigidity to the nucleus and maintain shape. Lamins also maintain chromosome positioning and play important roles in several nuclear processes like replication, DNA damage repair, transcription, and epigenetic modifications. LMNA mutations affect cardiac tissue, muscle tissues, adipose tissues to precipitate several diseases collectively termed as laminopathies. However, the rationale behind LMNA mutations and laminopathies continues to elude scientists. During interphase, several chromosomes form inter/intrachromosomal contacts inside nucleoplasm and several chromosomal loops also stretch out to make a 'loop-cluster' which are key players to regulate gene expressions. In this perspective, we have proposed that the lamin network in tandem with nuclear actin and myosin provide mechanical rigidity to the chromosomal contacts and facilitate loop-clusters movements. LMNA mutations thus might perturb the landscape of chromosomal contacts or loop-clusters positioning which can impair gene expression profile.
Topics: Animals; Cell Nucleus; Chromosome Positioning; Gene Expression Regulation; Humans; Lamin Type A; Mutation; Nuclear Lamina
PubMed: 32453974
DOI: 10.1080/19491034.2020.1769445 -
The Journal of Pharmacology and... Nov 2019In December 2018, the Centers for Disease Control declared fentanyl the deadliest drug in America. Opioid overdose is the single greatest cause of death in the United... (Review)
Review
In December 2018, the Centers for Disease Control declared fentanyl the deadliest drug in America. Opioid overdose is the single greatest cause of death in the United States adult population (ages 18-50), and fentanyl and its analogs [fentanyl/fentanyl analogs (F/FAs)] are currently involved in >50% of these deaths. Anesthesiologists in the United States were introduced to fentanyl in the early 1970s when it revolutionized surgical anesthesia by combining profound analgesia with hemodynamic stability. However, they quickly had to master its unique side effect. F/FAs can produce profound rigidity in the diaphragm, chest wall and upper airway within an extremely narrow dosing range. This clinical effect was called wooden chest syndrome (WCS) by anesthesiologists and is not commonly known outside of anesthesiology or to clinicians or researchers in addiction research/medicine. WCS is almost routinely fatal without expert airway management. This review provides relevant clinical human pharmacology and animal data demonstrating that the significant increase in the number of F/FA-induced deaths may involve -adrenergic and cholinergic receptor-mediated mechanical failure of the respiratory and cardiovascular systems with rapid development of rigidity and airway closure. Although morphine and its prodrug, heroin, can cause mild rigidity in abdominal muscles at high doses, neither presents with the distinct and rapid respiratory failure seen with F/FA-induced WCS, separating F/FA overdose from the slower onset of respiratory depression caused by morphine-derived alkaloids. This distinction has significant consequences for the design and implementation of new pharmacologic strategies to effectively prevent F/FA-induced death. SIGNIFICANCE STATEMENT: Deaths from fentanyl and F/FAs are increasing in spite of availability and awareness of the opioid reversal drug naloxone. This article reviews literature suggesting that naloxone may be ineffective against centrally mediated noradrenergic and cholinergic effects of F/FAs, which clinically manifest as severe muscle rigidity and airway compromise (e.g., wooden chest syndrome) that is rapid and distinct from respiratory depression seen with morphine-derived alkaloids. A physiologic model is proposed and implications for new drug development and treatment are discussed.
Topics: Adrenergic Neurons; Analgesics, Opioid; Drug Overdose; Fentanyl; Humans; Muscle Rigidity; Naloxone; Narcotic Antagonists; Opioid Epidemic; Respiratory Insufficiency; Time-to-Treatment
PubMed: 31492824
DOI: 10.1124/jpet.119.258566 -
Medicina (Kaunas, Lithuania) Aug 2023: Whiplash is associated with a wide variety of clinical manifestations, including headache, neck pain, cervical rigidity, shoulder and back pain, paresthesia, vertigo,... (Review)
Review
: Whiplash is associated with a wide variety of clinical manifestations, including headache, neck pain, cervical rigidity, shoulder and back pain, paresthesia, vertigo, and temporomandibular disorders (TMDs). Previous studies reported that TMDs are more common in individuals with chronic whiplash-associated disorders (WAD) than in the general population; however, the pathophysiology and mechanism of this relationship are still not well understood. : A PubMed and Ovid EMBASE review was performed to identify all studies addressing the trauma related cause and effect relationship between WAD and TMDs from January 2003 to March 2023. : After screening for eligibility and inclusion criteria, a total of 16 articles met the selection criteria. The various included studies discussed different aspects of the association between WDA and TMDs, including changes in the coordination and amplitude of jaw opening, the severity of the associated symptoms/signs in cases of WAD, the degree of fatigue and psychological stress, difficulty in feeding, cervical and myofascial pain, changes in the MRI signal at various muscle points, muscle tenderness, and quality of life. : In this review, we summarized the clinical evidence of any trauma related cause and effect relationship between whiplash and TMDs. An accurate screening of the previous literature showed that, in conclusion, the relationship between whiplash and TMDs is still unclear.
Topics: Humans; Quality of Life; Temporomandibular Joint Disorders; Neck; Fatigue; Headache
PubMed: 37629772
DOI: 10.3390/medicina59081482 -
Brain : a Journal of Neurology Sep 2023Although rigidity is a cardinal motor sign in patients with Parkinson's disease (PD), the instrumental measurement of this clinical phenomenon is largely lacking, and...
Although rigidity is a cardinal motor sign in patients with Parkinson's disease (PD), the instrumental measurement of this clinical phenomenon is largely lacking, and its pathophysiological underpinning remains still unclear. Further advances in the field would require innovative methodological approaches able to measure parkinsonian rigidity objectively, discriminate the different biomechanical sources of muscle tone (neural or visco-elastic components), and finally clarify the contribution to 'objective rigidity' exerted by neurophysiological responses, which have previously been associated with this clinical sign (i.e. the long-latency stretch-induced reflex). Twenty patients with PD (67.3 ± 6.9 years) and 25 age- and sex-matched controls (66.9 ± 7.4 years) were recruited. Rigidity was measured clinically and through a robotic device. Participants underwent robot-assisted wrist extensions at seven different angular velocities randomly applied, when ON therapy. For each value of angular velocity, several biomechanical (i.e. elastic, viscous and neural components) and neurophysiological measures (i.e. short and long-latency reflex and shortening reaction) were synchronously assessed and correlated with the clinical score of rigidity (i.e. Unified Parkinson's Disease Rating Scale-part III, subitems for the upper limb). The biomechanical investigation allowed us to measure 'objective rigidity' in PD and estimate the neuronal source of this phenomenon. In patients, 'objective rigidity' progressively increased along with the rise of angular velocities during robot-assisted wrist extensions. The neurophysiological examination disclosed increased long-latency reflexes, but not short-latency reflexes nor shortening reaction, in PD compared with control subjects. Long-latency reflexes progressively increased according to angular velocities only in patients with PD. Lastly, specific biomechanical and neurophysiological abnormalities correlated with the clinical score of rigidity. 'Objective rigidity' in PD correlates with velocity-dependent abnormal neuronal activity. The observations overall (i.e. the velocity-dependent feature of biomechanical and neurophysiological measures of objective rigidity) would point to a putative subcortical network responsible for 'objective rigidity' in PD, which requires further investigation.
Topics: Humans; Parkinson Disease; Muscle Rigidity; Reflex, Stretch; Reflex, Abnormal; Electromyography
PubMed: 37018058
DOI: 10.1093/brain/awad114 -
Frontiers in Aging Neuroscience 2021Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy are characterized by aggregation of abnormal α-synuclein (α-syn) and collectively referred... (Review)
Review
Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy are characterized by aggregation of abnormal α-synuclein (α-syn) and collectively referred to as α-synucleinopathy. Because these diseases have different prognoses and treatments, it is desirable to diagnose them early and accurately. However, it is difficult to accurately diagnose these diseases by clinical symptoms because symptoms such as muscle rigidity, postural dysreflexia, and dementia sometimes overlap among these diseases. The process of conformational conversion and aggregation of α-syn has been thought similar to that of abnormal prion proteins that cause prion diseases. In recent years, conversion methods, such as real-time quaking-induced conversion (RT-QuIC), have been developed. This method has succeeded in amplifying and detecting trace amounts of abnormal prion proteins in tissues and central spinal fluid of patients by inducing conversion of recombinant prion proteins shaking. Additionally, it has been used for antemortem diagnosis of prion diseases. Recently, aggregated α-syn has also been amplified and detected in patients by applying this method and many clinical studies have examined diagnosis using tissues or cerebral spinal fluid from patients. In this review, we discuss the utility and problems of α-syn RT-QuIC for antemortem diagnosis of α-synucleinopathies.
PubMed: 34650422
DOI: 10.3389/fnagi.2021.703984 -
Journal of Neurology Mar 2020The zona incerta has recently become an important target for deep-brain stimulation (DBS) in Parkinson's disease (PD). The present review summarizes clinical, animal and... (Review)
Review
The zona incerta has recently become an important target for deep-brain stimulation (DBS) in Parkinson's disease (PD). The present review summarizes clinical, animal and anatomical data which have indicated an important role of this structure in PD, and discusses potential mechanisms involved in therapeutic effects of DBS. Animal studies have suggested initially some role of neurons as well as GABAergic and glutamatergic receptors of the zona incerta in locomotion and generation of PD signs. Anatomical data have indicated that thanks to its multiple interconnections with the basal ganglia, thalamus, cerebral cortex, brainstem, spinal cord and cerebellum, the zona incerta is an important link in a neuronal chain transmitting impulses involved in PD pathology. Finally, clinical studies have shown that DBS of this structure alleviates parkinsonian bradykinesia, muscle rigidity and tremor. DBS of caudal zona incerta seemed to be the most effective therapeutic intervention, especially with regard to reduction of PD tremor as well as other forms of tremor.
Topics: Animals; Deep Brain Stimulation; Humans; Parkinson Disease; Zona Incerta
PubMed: 31375987
DOI: 10.1007/s00415-019-09486-8 -
Frontiers in Physiology 2021Parkinson's disease (PD) is a common neurodegenerative disorder classically characterized by symptoms of motor impairment (e.g., tremor and rigidity), but also... (Review)
Review
Parkinson's disease (PD) is a common neurodegenerative disorder classically characterized by symptoms of motor impairment (e.g., tremor and rigidity), but also presenting with important non-motor impairments. There is evidence for the reduced activity of both the parasympathetic and sympathetic limbs of the autonomic nervous system at rest in PD. Moreover, inappropriate autonomic adjustments accompany exercise, which can lead to inadequate hemodynamic responses, the failure to match the metabolic demands of working skeletal muscle and exercise intolerance. The underlying mechanisms remain unclear, but relevant alterations in several discrete central regions (e.g., dorsal motor nucleus of the vagus nerve, intermediolateral cell column) have been identified. Herein, we critically evaluate the clinically significant and complex associations between the autonomic dysfunction, fatigue and exercise capacity in PD.
PubMed: 33815139
DOI: 10.3389/fphys.2021.626640 -
Antioxidants (Basel, Switzerland) Oct 2020Currently, neurodegenerative diseases are a major cause of disability around the world. Parkinson's disease (PD) is the second-leading cause of neurodegenerative... (Review)
Review
Currently, neurodegenerative diseases are a major cause of disability around the world. Parkinson's disease (PD) is the second-leading cause of neurodegenerative disorder after Alzheimer's disease. In PD, continuous loss of dopaminergic neurons in the substantia nigra causes dopamine depletion in the striatum, promotes the primary motor symptoms of resting tremor, bradykinesia, muscle rigidity, and postural instability. The risk factors of PD comprise environmental toxins, drugs, pesticides, brain microtrauma, focal cerebrovascular injury, aging, and hereditary defects. The pathologic features of PD include impaired protein homeostasis, mitochondrial dysfunction, nitric oxide, and neuroinflammation, but the interaction of these factors contributing to PD is not fully understood. In neurotoxin-induced PD models, neurotoxins, for instance, 6-hydroxydopamine (6-OHDA), 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-Methyl-4-phenylpyridinium (MPP), paraquat, rotenone, and permethrin mainly impair the mitochondrial respiratory chain, activate microglia, and generate reactive oxygen species to induce autooxidation and dopaminergic neuronal apoptosis. Since no current treatment can cure PD, using a suitable PD animal model to evaluate PD motor symptoms' treatment efficacy and identify therapeutic targets and drugs are still needed. Hence, the present review focuses on the latest scientific developments in different neurotoxin-induced PD animal models with their mechanisms of pathogenesis and evaluation methods of PD motor symptoms.
PubMed: 33081318
DOI: 10.3390/antiox9101007