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05/Apr/2022

Case 1-2022: A 67-Year-Old Man with Motor Neuron Disease and Odd Behaviors during Sleep

A 67-year-old man with progressive motor neuron disease was evaluated in the sleep clinic because of dream enactment, daytime sleepiness, and apnea detected on a sleep study. Four months earlier, he had fallen asleep while washing dishes; this resulted in a fall and unstable C1 spinal fracture. A diagnostic test was performed.
Aleksandar Videnovic, M.D., Suma Babu, M.B., B.S., M.P.H., Brian Zhao, M.D., Haatem M. Reda, M.D., and Jenny J. Linnoila, M.D., Ph.D.

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18/Jan/2022

MPTP-induced mouse model of Parkinson’s disease: A promising direction of therapeutic strategies

Among the popular animal models of Parkinson’s disease (PD) commonly used in research are those that employ neurotoxins, especially 1-methyl- 4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). This neurotoxin exerts it neurotoxicity by causing a barrage of insults, such as oxidative stress, mitochondrial apoptosis, inflammation, excitotoxicity, and formation of inclusion bodies acting singly and in concert, ultimately leading to dopaminergic neuronal damage in the substantia nigra pars compacta and striatum. The selective neurotoxicity induced by MPTP in the nigrostriatal dopaminergic neurons of the mouse brain has led to new perspectives on PD. For decades, the MPTP-induced mouse model of PD has been the gold standard in PD research even though it does not fully recapitulate PD symptomatology, but it does have the advantages of simplicity, practicability, affordability, and fewer ethical considerations and greater clinical correlation than those of other toxin models of PD. The model has rejuvenated PD research and opened new frontiers in the quest for more novel therapeutic and adjuvant agents for PD. Hence, this review summarizes the role of MPTP in producing Parkinson-like symptoms in mice and the experimental role of the MPTP-induced mouse model. We discussed recent developments of more promising PD therapeutics to enrich our existing knowledge about this neurotoxin using this model.
Musa Mustapha, Che Norma Mat Taib
This work is licensed under a Creative Commons Attribution 4.0 International License30

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14/Sep/2021

Parkinson’s disease

Parkinson’s disease is a recognisable clinical syndrome with a range of causes and clinical presentations. Parkinson’s disease represents a fast-growing neurodegenerative condition; the rising prevalence worldwide resembles the many characteristics typically observed during a pandemic, except for an infectious cause. In most populations, 3–5% of Parkinson’s disease is explained by genetic causes linked to known Parkinson’s disease genes, thus representing monogenic Parkinson’s disease, whereas 90 genetic risk variants collectively explain 16–36% of the heritable risk of non-monogenic Parkinson’s disease. Additional causal associations include having a relative with Parkinson’s disease or tremor, constipation, and being a non-smoker, each at least doubling the risk of Parkinson’s disease. The diagnosis is clinically based; ancillary testing is reserved for people with an atypical presentation. Current criteria define Parkinson’s disease as the presence of bradykinesia combined with either rest tremor, rigidity, or both. However, the clinical presentation is multifaceted and includes many non-motor symptoms. Prognostic counselling is guided by awareness of disease subtypes. Clinically manifest Parkinson’s disease is preceded by a potentially long prodromal period. Presently, establishment of prodromal symptoms has no clinical implications other than symptom suppression, although recognition of prodromal parkinsonism will probably have consequences when disease-modifying treatments become available. Treatment goals vary from person to person, emphasising the need for personalised management. There is no reason to postpone symptomatic treatment in people developing disability due to Parkinson’s disease. Levodopa is the most common medication used as first-line therapy. Optimal management should start at diagnosis and requires a multidisciplinary team approach, including a growing repertoire of non-pharmacological interventions. At present, no therapy can slow down or arrest the progression of Parkinson’s disease, but informed by new insights in genetic causes and mechanisms of neuronal death, several promising strategies are being tested for disease-modifying potential. With the perspective of people with Parkinson’s disease as a so-called red thread throughout this Seminar, we will show how personalised management of Parkinson’s disease can be optimised.
  Bastiaan R Bloem, Michael S Okun, Christine Klein
© 2021 Elsevier Ltd. All rights reserved.


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