Peripheral markers in Parkinson's disease (PD) represent a hot issue to provide early diagnosis and assess disease progression. The gold standard marker of PD should feature the same reliability as the pathogenic alteration, which produces the disease itself. PD is foremost a movement disorder produced by a loss of nigrostriatal dopamine innervation, in which striatal dopamine terminals are always markedly reduced in PD patients to an extent, which never overlaps with controls. Similarly, a reliable marker of PD should possess such a non-overlapping feature when compared with controls. In the present study, we provide a novel pathological hallmark, the autophagosome, which in each PD patient was always suppressed compared with each control subject. Autophagosomes were counted as microtubule-associated proteins 1A/1B light chain 3B (LC3)-positive vacuoles at ultrastructural morphometry within peripheral (blood) blood mononuclear cells (PBMC). This also provides the gold standard to assess the autophagy status. Since autophagy may play a role in the pathogenesis of PD, autophagosomes may be a disease marker, while participating in the biology of the disease. Stoichiometric measurement of alpha-synuclein despite significantly increased in PD patients, overlapped between PD and control patients. Although the study need to be validated in large populations, the number of autophagy vacuoles is neither related with therapy (the amount was similarly suppressed in a few de novo patients), nor the age in PD or controls.

Biagioni, F., Ferese, R., Giorgi, F.s., Modugno, N., Olivola, E., Lenzi, P., et al. (2021). An attempt to dissect a peripheral marker based on cell pathology in Parkinson's disease. JOURNAL OF NEURAL TRANSMISSION, 128(10), 1599-1610 [10.1007/s00702-021-02364-6].

An attempt to dissect a peripheral marker based on cell pathology in Parkinson's disease

Olivola, Enrica;Gambardella, Stefano;Centonze, Diego;
2021-01-01

Abstract

Peripheral markers in Parkinson's disease (PD) represent a hot issue to provide early diagnosis and assess disease progression. The gold standard marker of PD should feature the same reliability as the pathogenic alteration, which produces the disease itself. PD is foremost a movement disorder produced by a loss of nigrostriatal dopamine innervation, in which striatal dopamine terminals are always markedly reduced in PD patients to an extent, which never overlaps with controls. Similarly, a reliable marker of PD should possess such a non-overlapping feature when compared with controls. In the present study, we provide a novel pathological hallmark, the autophagosome, which in each PD patient was always suppressed compared with each control subject. Autophagosomes were counted as microtubule-associated proteins 1A/1B light chain 3B (LC3)-positive vacuoles at ultrastructural morphometry within peripheral (blood) blood mononuclear cells (PBMC). This also provides the gold standard to assess the autophagy status. Since autophagy may play a role in the pathogenesis of PD, autophagosomes may be a disease marker, while participating in the biology of the disease. Stoichiometric measurement of alpha-synuclein despite significantly increased in PD patients, overlapped between PD and control patients. Although the study need to be validated in large populations, the number of autophagy vacuoles is neither related with therapy (the amount was similarly suppressed in a few de novo patients), nor the age in PD or controls.
2021
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/26 - NEUROLOGIA
English
Con Impact Factor ISI
Autophagy
LC3
Parkinson’s disease
Peripheral blood mononuclear cells
Synuclein
Vacuoles
Autophagy
Humans
Leukocytes, Mononuclear
Reproducibility of Results
alpha-Synuclein
Parkinson Disease
https://link.springer.com/article/10.1007/s00702-021-02364-6
Biagioni, F., Ferese, R., Giorgi, F.s., Modugno, N., Olivola, E., Lenzi, P., et al. (2021). An attempt to dissect a peripheral marker based on cell pathology in Parkinson's disease. JOURNAL OF NEURAL TRANSMISSION, 128(10), 1599-1610 [10.1007/s00702-021-02364-6].
Biagioni, F; Ferese, R; Giorgi, Fs; Modugno, N; Olivola, E; Lenzi, P; Gambardella, S; Centonze, D; Ruggieri, S; Fornai, F
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/282279
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