In Parkinson’s disease (PD) there is a preferential degeneration of neurons containing the dark-brown cytoplasmic pigment neuromelanin (NM), especially dopaminergic neurons of the substantia nigra the loss of which leads to the classical motor symptoms of PD. In humans, NM appears in early childhood and accumulates progressively with age, and increasing age is the main risk factor for developing PD. While the loss of pigmented nigral neurons in PD was first established a century ago and constitutes the cardinal pathologic diagnostic criteria for the disease, the potential contribution of NM to PD pathogenesis has remained largely unknown because, in contrast to humans, laboratory animal species commonly used in experimental research, such as rodents, lack NM. Thus, a factor so intimately linked to PD such as NM has been surprisingly neglected to date in experimental in vivo paradigms of the disease.

To overcome this major limitation, we developed the first genetically-engineered rodent model exhibiting age-dependent production and accumulation of human-like NM within PD-vulnerable nigral neurons, at levels up to those reached in elderly humans. Using this unique animal model, we found that progressive intracellular build-up of NM with age ultimately compromised neuronal function when allowed to accumulate above a specific threshold, eventually triggering in an age-dependent manner all the main pathological features of PD. Relevant to humans, intracellular NM levels reached this pathogenic threshold in PD patients and pre-PD subjects but not in healthy elderly individuals. Importantly, the lowering of intracellular NM by gene therapy to levels below this pathogenic threshold reversed PD symptoms and pathology in NM-producing rodents. These results suggest that progressive, age-dependent intracellular NM accumulation above a pathogenic threshold might be responsible for the initiation of PD. Accordingly, strategies to maintain or decrease intracellular NM to levels below its pathogenic threshold may provide unprecedented therapeutic opportunities to prevent, halt or delay neuronal dysfunction and degeneration linked to PD and, in a broader sense, brain aging.

Integrated Quantum Photonics allows the routing and control of single particles of light with intrinsically high stability and precision. However to date it has been limited to small-scale demonstrations in which only a small number of components are integrated on a chip. It is thus in high demand to scale up the integrated photonic circuits and increase the complexity and computational power of modern quantum information processing technologies that would enable many revolutionary applications. In fact, coherently and precisely controlling large quantum devices and complex multidimensional entanglement systems has been a challenging task owing to the complex interactions of correlated particles in large quantum systems.

In an international research effort led by scientists from the University of Bristol’s Quantum Engineering Technology Labs, we demonstrated the first ever large-scale integrated quantum photonic circuit, which can generate, control and analyze high-dimensional entanglement with unprecedented high precision and generality. A programmable bipartite path-encoded multidimensional entangled system with dimension up to 15×15 was demonstrated, where each photon exists over 15 optical paths at the same time and the two photons are entangled with each other there. This multidimensional entanglement system is achieved by scaling up the silicon-photonics quantum circuits via a single chip integration of 550 optical components including 16 identical photon-pair sources, 93 optical phase-shifters, 122 beam-splitters, among other optical elements. The quantum chip was realised using a scalable silicon photonics technology, similar to today’s electronic circuits, which would provide a path to manufacture massive components for the realization of an optical quantum computer. The work was a joint effort of the Peking University, the Technical University of Denmark, ICFO, the Max Planck Institute of Quantum Optics, the Polish Academy of Sciences (PAS) and the University of Copenhagen.