Primary cilia and ciliary signaling pathways in aging and age-related brain disorders.

Brain disorders are characterized by the progressive loss of structure and function of the brain as a consequence of progressive degeneration and/or death of nerve cells. Aging is a major risk factor for brain disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and stroke. Various cellular and molecular events have been shown to play a role in the progress of neurodegenerative diseases. Emerging studies suggest that primary cilia could be a key regulator in brain diseases. The primary cilium is a singular cellular organelle expressed on the surface of many cell types, such as astrocytes and neurons in the mature brain. Primary cilia detect extracellular cues, such as Sonic Hedgehog (SHH) protein, and transduce these signals into cells to regulate various signaling pathways. Abnormalities in ciliary length and frequency (ratio of ciliated cells) have been implicated in various human diseases, including brain disorders. This review summarizes current findings and thoughts on the role of primary cilia and ciliary signaling pathways in aging and age-related brain disorders.

The COVID-19 Pandemic: Reflections of Science, Person, and Challenge in Academic Research Settings.

In spring of 2021, the Society on NeuroImmune Pharmacology (SNIP) organized a virtual workshop on the coronavirus disease 2019 (COVID-19). The daylong event's fourth and final symposium, "Well-being and reflections," offered a glimpse at the pandemic's impact on the lives of our scientists and educators. This manuscript includes a brief summary of the symposium, a transcription of our incoming president Dr. Santosh Kumar's lecture, titled "Intervention and improved well-being of basic science researchers during the COVID-19 era: a case study," and the panel discussion that followed, "Reflection and sharing," featuring Drs. Jean M. Bidlack, Sylvia Fitting, Santhi Gorantla, Maria Cecilia G. Marcondes, Loyda M. Melendez, and Ilker K. Sariyer. The conclusion of this manuscript includes comments from SNIP's president Dr. Sulie L. Chang and our Chief Editor, Dr. Howard E. Gendelman. Drs. Sowmya Yelamanchili and Jeymohan Joseph co-chaired the symposium.

The Immunopathobiology of SARS-CoV-2 Infection.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to coronavirus disease 2019 (COVID-19). Virus-specific immunity controls infection, transmission and disease severity. With respect to disease severity, a spectrum of clinical outcomes occur associated with age, genetics, comorbidities and immune responses in an infected person. Dysfunctions in innate and adaptive immunity commonly follow viral infection. These are heralded by altered innate mononuclear phagocyte differentiation, activation, intracellular killing and adaptive memory, effector, and regulatory T cell responses. All of such affect viral clearance and the progression of end-organ disease. Failures to produce effective controlled antiviral immunity leads to life-threatening end-organ disease that is typified by the acute respiratory distress syndrome. The most effective means to contain SARS-CoV-2 infection is by vaccination. While an arsenal of immunomodulators were developed for control of viral infection and subsequent COVID-19 disease, further research is required to enable therapeutic implementation.

The Natural History, Pathobiology, and Clinical Manifestations of SARS-CoV-2 Infections.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of coronavirus disease 2019 (COVID-19). SARS-CoV-2, is a positive-sense single-stranded RNA virus with epithelial cell and respiratory system proclivity. Like its predecessor, SARS-CoV, COVID-19 can lead to life-threatening disease. Due to wide geographic impact affecting an extremely high proportion of the world population it was defined by the World Health Organization as a global public health pandemic. The infection is known to readily spread from person-to-person. This occurs through liquid droplets by cough, sneeze, hand-to-mouth-to-eye contact and through contaminated hard surfaces. Close human proximity accelerates SARS-CoV-2 spread. COVID-19 is a systemic disease that can move beyond the lungs by blood-based dissemination to affect multiple organs. These organs include the kidney, liver, muscles, nervous system, and spleen. The primary cause of SARS-CoV-2 mortality is acute respiratory distress syndrome initiated by epithelial infection and alveolar macrophage activation in the lungs. The early cell-based portal for viral entry is through the angiotensin-converting enzyme 2 receptor. Viral origins are zoonotic with genomic linkages to the bat coronaviruses but without an identifiable intermediate animal reservoir. There are currently few therapeutic options, and while many are being tested, although none are effective in curtailing the death rates. There is no available vaccine yet. Intense global efforts have targeted research into a better understanding of the epidemiology, molecular biology, pharmacology, and pathobiology of SARS-CoV-2. These fields of study will provide the insights directed to curtailing this disease outbreak with intense international impact. Graphical Abstract.