**Acknowledgements**

danger signals to cause inflammation mediated by the innate immune system. Recent studies have shown that mitochondrial DAMPs have the potential to mediate inflammatory signaling in the brain; therefore, its contribution to the neuroinflammatory process in neurodegenerative disorders characterized by impaired mitochondrial function represents an emerging and

Further understanding of neuronal innate immunity-induced chronic mild neuroinflammation and its impact on age-related neurodegenerative disorders should focus on new studies addressing not only mitochondrial dysfunction and protein oligomerization but also mild inflammation, nutritional states, among others. The development of new biomarkers focusing on the inflammatory process and the identification of protective inflammatory processes should be pursuit. Additionally, exploiting the effect of mutations, epigenetic and the microbiome on immune-related modifications affecting the AD and PD phenotypes will be of para-

**Figure 1.** Mitochondria are primary targets of cellular peptides, such as Aβ, tau and SNCA, overproduced during AD and PD pathogenesis. Damaged mitochondria are a source of DAMPs that activate the NLRP3 inflammasome and TLRs leading to the intraneuronal production of cytokines. These proinflammatory cytokines are released and activate innate immune response through microglia and astrocytes. This chronic inflammation impacts neurons exacerbating peptides

promising field of research (**Figure 1**).

152 Mitochondrial Diseases

formation and mitochondrial damage.

mount relevance to understand etiology of both diseases.

Work in our laboratories is supported by Fundação para a Ciência e a Tecnologia (FCT) and by EU-FEDER funding through the Operational Competitiveness Programme—COMPETE grant UID/NEU/04539/2013 and by Prémio Santa Casa Neurociências Mantero Belard MB-40-2016.
