{"id":317445,"date":"2026-02-03T03:56:08","date_gmt":"2026-02-03T03:56:08","guid":{"rendered":"https:\/\/www.europesays.com\/ie\/317445\/"},"modified":"2026-02-03T03:56:08","modified_gmt":"2026-02-03T03:56:08","slug":"immunotherapy-blocking-microglial-fc%ce%b3r-prevents-neuron-loss-in-parkinsons-disease","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/ie\/317445\/","title":{"rendered":"Immunotherapy Blocking Microglial Fc\u03b3R Prevents Neuron Loss in Parkinson\u2019s Disease"},"content":{"rendered":"

\"Neurons<\/a>Credit: koto_feja \/ Getty Images<\/p>\n

Parkinson\u2019s disease<\/a> (PD) is defined by the progressive loss of dopaminergic neurons in the substantia nigra, but the biological forces that push these neurons toward degeneration remain only partly understood. Microglia\u2014the brain\u2019s resident immune cells\u2014have long been implicated in this process. They become reactive early in disease, cluster around vulnerable neurons, and release inflammatory factors. Yet the precise trigger that converts microglia from protective sentinels into active participants in neuronal destruction has remained elusive.<\/p>\n

A new study published in npj Parkinson\u2019s Disease, \u201cMicroglial low-affinity Fc\u03b3R mediates the phagocytic elimination of dopaminergic neurons in Parkinson\u2019s disease degeneration<\/a>,\u201d offers a mechanistic explanation. Researchers at the Institut de Neuroci\u00e8ncies of the Universitat Aut\u00f2noma de Barcelona (INc\u2011UAB) and the UAB department of biochemistry and molecular biology report that microglia in PD appear to eliminate dopaminergic neurons through an Fc gamma receptor (Fc\u03b3R)\u2013driven phagocytic program\u2014and that blocking this receptor with immunotherapy can prevent neuron loss in disease models.<\/p>\n

The team began by examining postmortem brain tissue from PD patients. As expected, the substantia nigra contained a high proportion of reactive microglia, consistent with chronic neuroinflammation. But a more striking finding emerged: these reactive microglia expressed elevated levels of low\u2011affinity Fc\u03b3 receptors (CD16 and CD32). These receptors normally help immune cells identify damaged or antibody\u2011tagged targets for clearance. In PD, however, the researchers propose that Fc\u03b3Rs may be misidentifying still\u2011viable dopaminergic neurons as debris.<\/p>\n

This pattern was mirrored in the MPTP mouse model of PD, where microglia also upregulated Fc\u03b3Rs and physically engaged degenerating dopaminergic neurons. Prior work from the same group had shown that microglia make direct body\u2011to\u2011body contact with vulnerable neurons before their disappearance, suggesting an active phagocytic process rather than passive degeneration.<\/p>\n

To test whether Fc\u03b3Rs were driving this elimination, the researchers turned to both in vitro and in vivo systems. In co\u2011cultures modeling an interferon\u2011\u03b3\u2013driven inflammatory environment, microglia readily engulfed dopaminergic cells\u2014but this phagocytosis was sharply reduced when Fc\u03b3Rs were blocked with neutralizing antibodies. In parallel, inhibiting Cdc42, a cytoskeletal regulator downstream of Fc\u03b3R signaling, also prevented microglia from forming the actin\u2011rich \u201cphagocytic cup\u201d required to engulf neurons.<\/p>\n

\u201cFinally, passive immunotherapy using CD16\/32 neutralizing monoclonal antibodies in MPTP-treated mice protected DA neurons from elimination, suggesting a novel and viable potential therapeutic strategy for PD,\u201d the authors wrote. This intervention preserved dopaminergic neurons even under conditions of intense neuroinflammation.<\/p>\n

\u201cWhat is particularly interesting is that in animal and cellular models of the disease, blocking Fc gamma receptors with immunotherapy, as well as pharmacologically inhibiting Cdc42, significantly reduced the elimination of dopaminergic neurons, preserving them even under conditions of intense neuroinflammation,\u201d said corresponding author Carlos Barcia, PhD, from UAB.<\/p>\n

Together, the findings position Fc\u03b3R\u2011mediated phagocytosis as a central mechanism of dopaminergic neuron loss in PD\u2014and highlight microglial Fc\u03b3R as a promising immunotherapeutic target. While the work remains preclinical, it opens a new translational path: instead of trying to rescue neurons after they degenerate, future therapies might prevent microglia from mistakenly \u201ceating\u201d them in the first place.<\/p>\n","protected":false},"excerpt":{"rendered":"Credit: koto_feja \/ Getty Images Parkinson\u2019s disease (PD) is defined by the progressive loss of dopaminergic neurons in…\n","protected":false},"author":2,"featured_media":317446,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[74],"tags":[18,19,97383,4701,17,81909,75474,5,18862,54001,82,5632,39996],"class_list":{"0":"post-317445","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-technology","8":"tag-eire","9":"tag-ie","10":"tag-immune-cells","11":"tag-immunotherapy","12":"tag-ireland","13":"tag-monoclonal-antibodies","14":"tag-mouse","15":"tag-news","16":"tag-parkinsons-disease","17":"tag-phagocytosis","18":"tag-technology","19":"tag-topics","20":"tag-translational-medicine"},"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@ie\/116004689283887828","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts\/317445","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/comments?post=317445"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts\/317445\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/media\/317446"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/media?parent=317445"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/categories?post=317445"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/tags?post=317445"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}