Unraveling the mystery: How autophagy deficiency in dopaminergic neurons drives human Parkinson’s disease
Abstract Alpha-synuclein (α-synuclein), a key component of Lewy body pathology, is a classical hallmark of Parkinson’s disease. In previous studies, our group has examined dopaminergic neuron-specific Atg7 autophagy-deficient mice, observing α-synuclein aggregation in vivo. This pathological process...
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BMC
2025-07-01
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| Series: | Molecular Brain |
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| Online Access: | https://doi.org/10.1186/s13041-025-01235-5 |
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| author | Sachiko Noda Nobutaka Hattori |
| author_facet | Sachiko Noda Nobutaka Hattori |
| author_sort | Sachiko Noda |
| collection | DOAJ |
| description | Abstract Alpha-synuclein (α-synuclein), a key component of Lewy body pathology, is a classical hallmark of Parkinson’s disease. In previous studies, our group has examined dopaminergic neuron-specific Atg7 autophagy-deficient mice, observing α-synuclein aggregation in vivo. This pathological process led to dopamine neuron loss and age-related motor impairments. Further, in a recent study, we developed a new mouse model by crossing human α-synuclein bacterial artificial chromosome transgenic mice with dopaminergic neuron-specific Atg7 conditional knockout mice to further investigate these mechanisms. These model mice exhibited accelerated Lewy body-like pathology and motor dysfunction, providing additional evidence that autophagy deficiency exacerbates synuclein toxicity in vivo. This nano-review provides essential clues that autophagy deficiency in dopamine neurons may contribute to the onset of human synuclein diseases. |
| format | Article |
| id | doaj-art-12adbe5d04da443e9109993a96e10b7c |
| institution | Kabale University |
| issn | 1756-6606 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Brain |
| spelling | doaj-art-12adbe5d04da443e9109993a96e10b7c2025-08-20T03:46:28ZengBMCMolecular Brain1756-66062025-07-011811310.1186/s13041-025-01235-5Unraveling the mystery: How autophagy deficiency in dopaminergic neurons drives human Parkinson’s diseaseSachiko Noda0Nobutaka Hattori1Department of Neurology, Juntendo University Graduate School of MedicineDepartment of Neurology, Juntendo University Graduate School of MedicineAbstract Alpha-synuclein (α-synuclein), a key component of Lewy body pathology, is a classical hallmark of Parkinson’s disease. In previous studies, our group has examined dopaminergic neuron-specific Atg7 autophagy-deficient mice, observing α-synuclein aggregation in vivo. This pathological process led to dopamine neuron loss and age-related motor impairments. Further, in a recent study, we developed a new mouse model by crossing human α-synuclein bacterial artificial chromosome transgenic mice with dopaminergic neuron-specific Atg7 conditional knockout mice to further investigate these mechanisms. These model mice exhibited accelerated Lewy body-like pathology and motor dysfunction, providing additional evidence that autophagy deficiency exacerbates synuclein toxicity in vivo. This nano-review provides essential clues that autophagy deficiency in dopamine neurons may contribute to the onset of human synuclein diseases.https://doi.org/10.1186/s13041-025-01235-5Parkinson’s diseaseΑ-synucleinAutophagyDopaminergic neurons |
| spellingShingle | Sachiko Noda Nobutaka Hattori Unraveling the mystery: How autophagy deficiency in dopaminergic neurons drives human Parkinson’s disease Molecular Brain Parkinson’s disease Α-synuclein Autophagy Dopaminergic neurons |
| title | Unraveling the mystery: How autophagy deficiency in dopaminergic neurons drives human Parkinson’s disease |
| title_full | Unraveling the mystery: How autophagy deficiency in dopaminergic neurons drives human Parkinson’s disease |
| title_fullStr | Unraveling the mystery: How autophagy deficiency in dopaminergic neurons drives human Parkinson’s disease |
| title_full_unstemmed | Unraveling the mystery: How autophagy deficiency in dopaminergic neurons drives human Parkinson’s disease |
| title_short | Unraveling the mystery: How autophagy deficiency in dopaminergic neurons drives human Parkinson’s disease |
| title_sort | unraveling the mystery how autophagy deficiency in dopaminergic neurons drives human parkinson s disease |
| topic | Parkinson’s disease Α-synuclein Autophagy Dopaminergic neurons |
| url | https://doi.org/10.1186/s13041-025-01235-5 |
| work_keys_str_mv | AT sachikonoda unravelingthemysteryhowautophagydeficiencyindopaminergicneuronsdriveshumanparkinsonsdisease AT nobutakahattori unravelingthemysteryhowautophagydeficiencyindopaminergicneuronsdriveshumanparkinsonsdisease |