Imaging of neuroinflammation

Abstract

For those of us interested in molecular imaging of the majorneurodegenerative disorders, the last decade has witnessed amarked advancement. From basic research to clinical studies,the field has evolved using multidisciplinary techniques andskills, leading to results of significant clinical interest.Reasoning on the role of inflammation in neurodegenerativedisease, the recentpaper by Santillo et al. [ 1]isanexampleofthe breadth and depth of the evolving impact of molecularimaging on the field of neurodegeneration and stimulates areflection on the state of the art of target-specific positronemission tomography (PET) probes of inflammation for brainimaging.Inflammation in neurodegenerative diseaseReactive astrogliosis is a ubiquitous hallmark of all centralnervous system (CNS) pathologies. Chronic neuroinflamma-tion is associated with a broad range of neurodegenerativediseases, including Alzheimer’s disease (AD), Parkinson’sdisease (PD), amyotrophic lateral sclerosis (ALS), spinalmuscular atrophy (SMA), Huntington’s disease (HD) and allof the tauopathies [2]. Although the key of molecular andcellular events underlying development of different neurode-generative disorders is clearly divergent, it should be pointedout that death of neurons depends on activation of residentmicroglial populations in specific brain regions. Up to nowsome of the molecular and cellular mechanisms of neuro-degeneration have been clearly identified.Neurodegenerative diseases are often characterized byintraneuronalaswellasextracellularaccumulationoffibrillarymaterials. Formation of intracellularinclusionbodies resultingfrom aberrant protein folding, abnormal protein-protein inter-actions and/or dysregulation of the ubiquitin-proteasomesystem (UPS) are thought to play a principal role in neuronaldysfunction and death of neurons that characterizes severalcommon neurodegenerative diseases [3].Brain-resident macrophages (microglia) activation plays acritical role in normal brain function by mediating innateimmune responses and are the primary mediators of neuro-inflammatory responses. Astrocytes, highly differentiatedcells widely distributed in the entire CNS, contribute to everymajor aspect of brain development, function and disease suchas regulation of cerebral blood flow and maintenance ofsynaptic function, neuronal metabolism and neurotransmittersynthesis [4]. Along with other glial cells such as oligoden-drocytes and microglia, astrocytes respond to all forms ofCNS insults such as infection, trauma and ischaemia by aprocess commonly referred to as reactive astrogliosis, whichinvolves changes in their molecular expression and mor-phology [2]. The growing body of evidence on the roleinflammation in neurodegenerative diseases stimulated thedemand for imaging modalities for the evaluation ofinflammation in human brain, which is the topic of thiseditorial “Imaging of neuroinflammation”. Some specificproinflammatory factors have been brought to the attentionof scientists as possible targets for molecular imaging probes.Translocator protein systemTranslocator protein (TSPO) previously known as the periph-eral benzodiazepine receptor is an 18 kDa protein located onthe outer membrane of mitochondria overexpressed byactivated microglia. TSPO is directly or indirectly involvedinmanyfunctions,includingregulationofcholesteroltransport[5], synthesis of steroid hormones [6] and apoptosis [7].TSPOisexpressedonlyatlow levelsinthehealthyhumanbrain. Increased expression has been observed using the