Maria Grazia Spillantini - Selected Publications#

SPILLANTINI MG, Schmidt ML, Lee V M-Y, Trojanowski JQ, Jakes R, Goedert M. Alpha-ynuclein in Lewy bodies. (1997) Nature 388: 839-840.

First report describing alpha-synuclein in Lewy bodies in Parkinson's disease.

SPILLANTINI MG, Crowther RA, Jakes R, Hasegawa M, Goedert M α-Synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with Lewy bodies. (1998) Proc Natl Acad Sci USA 95 (11), 6469-6473.

First demonstration that alpha-synuclein is the component of the filaments that form the Lewy bodies in Parkinson's disease and glia cytoplasmic inclusions in multiple system atrophy.

SPILLANTINI MG, Murrell JR, Goedert M, Farlow MR, Klug A, Ghetti B. Mutation in the tau gene in familial multiple system tauopathy with presenile dementia. (1998) Proc Natl Acad Sci USA 95: 7737-7741.

One of the first mutations in the MAPT gene identified as cause of familial forms of Frontotemporal Dementia and Parkinsonism linked to chromosome 17. The finding established the role of the microtubuile associated protein tau in neurodegenerative diseases.

Garcia Reitböck P, Anichtchik O, Bellucci A, Iovino M, Ballini C, Fineberg E, Ghetti B, Della Corte L, Spano PF, Tofaris G K, Goedert M, SPILLANTINI MG. SNARE protein redistribution and synaptic failure in a mouse model of Parkinson’s disease. (2010) Brain 133: 2032-2044. First demonstration of SNARE protein redistribution and association with alpha-synuclein aggregates in the striatum of transgenic alpha-synuclein mice and human Parkinson's disease patients.

Sidoryk-Wegrzynowicz M, Gerber YN, Ries M, Sastre M, Tolkovsky AM, Spillantini MG. Astrocytes in mouse models of tauopathies acquire early deficits and lose neurosupportive functions. Acta Neuropathol Commun. 2017 Nov 29;5(1):89. doi: 10.1186/s40478-017-0478-9.

Demonstration that astrocytes in brain of P301S tau transgenic mice become dysfunctional and lose their ability to support neurones, even before tau aggregates form.

Brelstaff J, Tolkovsky AM, Ghetti B, Goedert M, SPILLANTINI MG. Living Neurons with Tau Filaments Aberrantly Expose Phosphatidylserine and Are Phagocytosed by Microglia. Cell Rep. 2018 Aug 21;24(8):1939-1948.e4.

First demonstration that in tauopathy neurones containing tau aggregates attract microglia that then phagocytose them while still alive.

Wegrzynowicz M, Bar-On D, Calo' L, Anichtchik O, Iovino M, Xia J, Ryazanov S, Leonov A, Giese A, Dalley JW, Griesinger C, Ashery U, SPILLANTINI MG. Depopulation of dense α-synuclein aggregates is associated with rescue of dopamine neuron dysfunction and death in a new Parkinson's disease model. Acta Neuropathol. (2019) 138: 575-595.

Description of a new mouse model expressing aggregation prone alpha-synuclein in dopaminergic neurons and showing progressive aggregation of alpha-synuclein, dopaminergic dysfunction and dopaminergic neuronal death associated with movement alterations. For the first time aggregates formation is monitored by superresolution microscopy. An oligomer modifier is tested and its effect on the aggregates monitored by superresolution microscopy. The oligomer modifier treatment prevents dopaminergic dysfunction and neuron death. Based on these data the compound is now in Phase 2 Clinical Trials in human patients.

Brelstaff JH, Mason M, Katsinelos T, McEwan WA, Ghetti B, Tolkovsky AM, SPILLANTINI MG. Microglia become hypofunctional and release metalloproteases and tau seeds when phagocytosing live neurons with P301S tau aggregates. Sci Adv. 2021 Oct 22;7(43):eabg4980 This is the first demonstration that microglia in a transgenic mouse model of tau aggregation following phagocytose of neurones containing tau aggregates becomes senescent and release tau seeds becoming a vehicle of tau spreading.
Caló L, Hidari E, Wegrzynowicz M, Dalley JW, Schneider BL, Podgajna M, Anichtchik O, Carlson E, Klenerman D, Spillantini MG. CSPα reduces aggregates and rescues striatal dopamine release in α-synuclein transgenic mice. Brain. 2021 Jul 28;144(6):1661-1669. This study shows that CSPa is reduced in the striatal synapse of alpha-synuclein transgenic mice and its increase rescues synaptic dysfunction due to alpha-synuclein aggregation. This paper further strenghten the idea that alpha-synuclein aggregation at the synapse is the initial pathological step in Parkinson's disease.

Vivacqua G, Mason M, De Bartolo MI, Węgrzynowicz M, Calò L, Belvisi D, Suppa A, Fabbrini G, Berardelli A, Spillantini M. Salivary α-Synuclein RT-QuIC Correlates with Disease Severity in de novo Parkinson's Disease. Mov Disord. 2022 Oct 19. doi: 10.1002/mds.29246.

Demonstration that salivary α-synuclein RT-QuiC correlates with diseases severity in newly diagnosed Parkinson's patients.