A novel FBXO7-R345P mutation in a Chinese family with autosomal recessive parkinsonian-pyramidal syndrome

Wang, Zhanjun; Yang, Song; Zhu, Wenjia; Xl, Wang; Li, Xuying; Xu, Fanxi; Si, Lianghao; Yao, Tingyan; Zhu, Jingxian; Li, Hong; Wei, Li; Lin, Feng; Wang, Chaodong

doi:10.1016/j.parkreldis.2021.06.005

Cited by 3 publications

(1 citation statement)

References 13 publications

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“…Parkinson disease (PD) and parkinsonism‐related disorders have been associated with genetic mutations in PARK loci. Among those, mutations in PARK15 which encodes for FBXO7, have been associated with a recessive and complicated subtype of parkinsonism termed Parkinsonian Pyramidal syndrome (PPS) or PARK15 syndrome (Correa‐Vela et al, 2020; Di Fonzo et al, 2009; Jin et al, 2020; Lohmann et al, 2015; Lorenzo‐Betancor et al, 2020; Shojaee et al, 2008; Wang et al, 2021; Wei et al, 2018; Yalcin‐Cakmakli et al, 2014; Yoo et al, 2020; Zhao et al, 2020). Affected individuals with PARK15 mutations develop the disease as early as in their teens and present with a wide spectrum of signs and symptoms.…”

Section: Introductionmentioning

confidence: 99%

Loss of the parkinsonism‐associated protein FBXO7 in glutamatergic forebrain neurons in mice leads to abnormal motor behavior and synaptic defects

Wang,

Joseph,

Vingill

et al. 2023

Journal of Neurochemistry

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Mutations in PARK15, which encodes for the F‐box protein FBXO7 have been associated with Parkinsonian Pyramidal syndrome, a rare and complex movement disorder with Parkinsonian symptoms, pyramidal tract signs and juvenile onset. Our previous study showed that systemic loss of Fbxo7 in mice causes motor defects and premature death. We have also demonstrated that FBXO7 has a crucial role in neurons as the specific deletion in tyrosine hydroxylase‐positive or glutamatergic forebrain neurons leads to late‐onset or early‐onset motor dysfunction, respectively. In this study, we examined NEX‐Cre;Fbxo7fl/fl mice, in which Fbxo7 was specifically deleted in glutamatergic projection neurons. The effects of FBXO7 deficiency on striatal integrity were investigated with HPLC and histological analyses. NEX‐Cre;Fbxo7fl/fl mice revealed an increase in striatal dopamine concentrations, changes in the glutamatergic, GABAergic and dopaminergic pathways, astrogliosis and microgliosis and little or no neuronal loss in the striatum. To determine the effects on the integrity of the synapse, we purified synaptic membranes, subjected them to quantitative mass spectrometry analysis and found alterations in the complement system, endocytosis and exocytosis pathways. These neuropathological changes coincide with alterations in spontaneous home cage behavior. Taken together, our findings suggest that FBXO7 is crucial for corticostriatal projections and the synaptic integrity of the striatum, and consequently for proper motor control.image

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Section: Introductionmentioning

confidence: 99%

Loss of the parkinsonism‐associated protein FBXO7 in glutamatergic forebrain neurons in mice leads to abnormal motor behavior and synaptic defects

Wang,

Joseph,

Vingill

et al. 2023

Journal of Neurochemistry

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The characteristics of FBXO7 and its role in human diseases

Zhong

et al. 2023

Gene

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The autophagy–lysosome pathway: a potential target in the chemical and gene therapeutic strategies for Parkinson’s disease

Jiao,

Meng,

et al. 2024

Neural Regeneration Research

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Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such as α-synuclein in neurons. As one of the major intracellular degradation pathways, the autophagy-lysosome pathway plays an important role in eliminating these proteins. Accumulating evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance of α-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s disease. Moreover, multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome pathway. Thus, this pathway appears to be a promising therapeutic target for treatment of Parkinson’s disease. In this review, we briefly introduce the machinery of autophagy. Then, we provide a description of the effects of Parkinson’s disease-related genes on the autophagy-lysosome pathway. Finally, we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy-lysosome pathway and their applications in Parkinson’s disease.

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A novel FBXO7-R345P mutation in a Chinese family with autosomal recessive parkinsonian-pyramidal syndrome

Cited by 3 publications

References 13 publications

Loss of the parkinsonism‐associated protein FBXO7 in glutamatergic forebrain neurons in mice leads to abnormal motor behavior and synaptic defects

Loss of the parkinsonism‐associated protein FBXO7 in glutamatergic forebrain neurons in mice leads to abnormal motor behavior and synaptic defects

The characteristics of FBXO7 and its role in human diseases

The autophagy–lysosome pathway: a potential target in the chemical and gene therapeutic strategies for Parkinson’s disease

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