Common and rare variants in HFE are not associated with Parkinson's disease in Europeans

Saini, Prabhjyot; Bandrés‐Ciga, Sara; Alcantud, Jose Luis; Ruz, Clara; Postuma, Ronald B.; Gan‐Or, Ziv

doi:10.1016/j.neurobiolaging.2021.05.019

Cited by 2 publications

(1 citation statement)

References 15 publications

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“…Parkinson’s disease (PD) is a common neurodegenerative disease of the central nervous system in which the selective loss of dopamine (DA) neurons in the substantia nigra leads to the exhaustion of DA released from the nerve endings of the striatum [ 1 , 2 ], which causes clinical motor symptoms that mainly manifest as resting tremors, muscle stiffness, and slow movement [ 3 , 4 ]. Moreover, PD is accompanied by nonmotor symptoms, such as hypoosmia, gastrointestinal dysfunction, cardiovascular dysfunction, sleep disturbance and neurocognitive dysfunction [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Safranal exerts a neuroprotective effect on Parkinson’s disease with suppression of NLRP3 inflammation activation

Yang,

Wei,

Sun

et al. 2024

Mol Biol Rep

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Background Parkinson’s disease (PD) is a common central nervous system neurodegenerative disease. Neuroinflammation is one of the significant neuropathological hallmarks. As a traditional Chinese medicine, Safranal exerts anti-inflammatory effects in various diseases, however, whether it plays a similar effect on PD is still unclear. The study was to investigate the effects and mechanism of Safranal on PD. Methods The PD mouse model was established by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine MPTP firstly. Next, the degree of muscle stiffness, neuromuscular function, motor retardation and motor coordination ability were examined by observing and testing mouse movement behavior. Immunofluorescence staining was used to observe the expression of tyrosine hydroxylase (TH). The dopamine (DA) content of the striatum was detected by High-performance liquid chromatography (HPLC). The expression of TH and NLRP3 inflammasome-related markers NLRP3, IL-1β, and Capase-1 were detected by Real-time Polymerase Chain Reaction (qRT-PCR) and western blotting (WB) respectively. Results Through behavioral testing, Parkinson’s mouse showed a higher muscle stiffness and neuromuscular tension, a more motor retardation and activity disorders, together with a worse motor coordination compared with sham group. Simultaneously, DA content and TH expression in the striatum were decreased. However, after using Safranal treatment, the above pathological symptoms of Parkinson’s mouse all improved compared with Safranal untreated group, the DA content and TH expression were also increased to varying degrees. Surprisingly, it observed a suppression of NLRP3 inflammation in the striatum of Parkinson’s mouse. Conclusions Safranal played a neuroprotective effect on the Parkinson’s disease and its mechanism was related to the inhibition of NLRP3 inflammasome activation.

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Section: Introductionmentioning

confidence: 99%

Safranal exerts a neuroprotective effect on Parkinson’s disease with suppression of NLRP3 inflammation activation

Yang,

Wei,

Sun

et al. 2024

Mol Biol Rep

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HFE Mutations in Neurodegenerative Disease as a Model of Hormesis

Marshall Moscon,

Connor

2024

IJMS

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Common variants in the iron regulatory protein HFE contribute to systematically increased iron levels, yet the effects in the brain are not fully characterized. It is commonly believed that iron dysregulation is a key contributor to neurodegenerative disease due to iron’s ability to catalyze reactive oxygen species production. However, whether HFE variants exacerbate or protect against neurodegeneration has been heavily debated. Some claim that mutated HFE exacerbates oxidative stress and neuroinflammation, thus predisposing carriers to neurodegeneration-linked pathologies. However, H63D HFE has also been shown to slow the progression of multiple neurodegenerative diseases and to protect against environmental toxins that cause neurodegeneration. These conflicting results showcase the need to further understand the contribution of HFE variants to neurodegenerative disease heterogeneity. Data from mouse models consistently demonstrate robust neuroprotection against toxins known to increase the risk of neurodegenerative disease. This may represent an adaptive, or hormetic, response to increased iron, which leaves cells better protected against future stressors. This review describes the current research regarding the contribution of HFE variants to neurodegenerative disease prognosis in the context of a hormetic model. To our knowledge, this is the first time that a hormetic model for neurodegenerative disease has been presented.

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Common and rare variants in HFE are not associated with Parkinson's disease in Europeans

Cited by 2 publications

References 15 publications

Safranal exerts a neuroprotective effect on Parkinson’s disease with suppression of NLRP3 inflammation activation

Safranal exerts a neuroprotective effect on Parkinson’s disease with suppression of NLRP3 inflammation activation

HFE Mutations in Neurodegenerative Disease as a Model of Hormesis

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