Table 2.

Synucleinopathy-associated pathogenesis in PFF culture studies.

Authors	Year	Comparator	Findings	Culture Age	PFF Species
Volpicelli-Daley et al.48	2011	Hippocampal neurons with and without α-syn aggregates	Decreased expression of multiple synaptic proteins. Impairments in neuronal excitability and connectivity.	E16-E18 mouse	Mouse
Volpicelli-Daley et al.49	2014	Hippocampal neurons with and without α-syn aggregates	Impairment of axonal transport of RAB7 and TrkB- containing endosomes and autophagosomes. Accumulation of pERK5.	E16-E18 mouse	Mouse
Tapias et al.54	2017	Mesencephalic dopamine neurons with and without α-syn aggregates	Decreased expression of synaptic proteins. Alterations in axonal transport-related proteins. Impaired mitochondria. Increased oxidative stress.	E17 rat	Human
Froula et al.58	2018	Hippocampal neurons with and without α-syn aggregates	Decreased mushroom spine density. Increased excitatory postsynaptic currents. Increased presynaptic docked vesicles. Decreased frequency and amplitude of spontaneous calcium transients.	E16-E18 mouse	Mouse
Grassi et al.56	2018	Hippocampal neurons with and without α-syn aggregates	pSyn* induces mitochondrial toxicity and fission, energetic stress and mitophagy.	E16-E18 mouse	Mouse
Wu et al.59	2019	Hippocampal neurons with and without α-syn aggregates	Decreased excitatory postsynaptic current frequency. Altered dendritic spines.	E16-E18 mouse	Human
Wang et al.57	2019	Cortical neurons with and without α-syn aggregates	Deficits in mitochondrial respiration	P1 mouse and rat	Mouse
Mahul-Mellier et al.55	2020	Hippocampal neurons with and without α-syn aggregates	Transcriptomic changes over time: D7: 75 total genes (27 upregulated, 48 downregulated) encoding for proteins located within synapses, axons, or secretory and exocytic vesicles. Genes encoding for proteins involved in neurogenesis and the organization, growth, and the extension of the axons and dendrites D14: 329 total genes (106 upregulated, 223 downregulated) linked to the synaptic, neuritic, and vesicular cellular compartments. Genes associated with neurogenesis, calcium homeostasis, synaptic homeostasis, cytoskeleton organization, response to stress, and neuronal cell death process. D21: 1017 total genes (455 upregulated, 562 downregulated) with enrichment in genes encoding for proteins related to the ion channel complex, plasma membrane protein complex, cell–cell junctions, synaptic functions, response to oxidative stress and mitochondria. D14 vs. D21: Differential expression of genes associated with mitochondrial and synaptic functions.	P0 mouse	Mouse

D day in vitro. Culture age animal age animals at the time of primary neurons harvest.